Various congenital defects in the eye which have been produced by interference with development at various stages of the embryonal growth may mimic the clinical picture of congenital corneal dystrophy which has not aroused much interest. Indeed, the literature1"3 apparently includes only three histopathological reports of congenital hereditary corneal dystrophy; the ultrastructural pathology of the condition has been explored recently.4'5.
In this study three such patients, two of them in the same family, were observed. A corneal button from each has been studied by light microscopy. This paper proposes to illustrate these cases and discuss the conditions which this defect may simulate.
A female child, aged 8 years, sought consultation in the ophthalmic department of Jipmer Hospital in November 1968, with the complaints of diminished vision and corneal opacities since early childhood. The parents had noticed the corneal haziness in the child at birth. Personal and family history revealed that the child was delivered at full term. The milestones of development were normal. The eyes of the parents were examined and were found normal. A history of consanguinity was present in the parents1 heredity (Fig. 1). The younger child (male), aged 2 years, showed similar haziness of the cornea in both eyes, but it was less intense. He also exhibited no photophobia and the haziness had been present since birth. There was no skeletal abnormality on physical examination. The liver and spleen were not palpable.
Case I & II: The female child aged 8 years exhibited no photophobia and was free from noticeable inflammation or nystagmus. Corneal diameter measured 10.5 mm in the horizontal meridian in both eyes. The intraocular pressures were normal (23.5 mm Hg with 7.5 gm weight under general anesthesia). Both corneas were steamy and completely hazy, the entire thickness and circumference being involved (Fig. 2). There was epithelial bedewing and no vascularization was seen in the peripheral corneal stroma. The corneal sensitivity was normal.
On slit-lamp examination, the corneal epithelium was edematous and roughened. The stromal thickening was evidently due to edema. The density of the corneal opacity did not permit clear (Visualization of deeper layers of the cornea. The epithelial edema did npt clear appreciably even with 50 per cent glycerine. However, the anterior chamber appeared normal, and the pupil was round and reacted to light.
The visual acuity was reduced to 2/60 in each eye without any glasses. The fundus was not clearly seen but. no gross abnormality was detected. The VDRL was negative. X-rays of skull, wrist, and chest were normal. The diagnosis of congenital hereditary corneal dystrophy was suspected. In December 1968, the patient's ocular condition was essentially unchanged. A 6 mm partial keratectomy was performed and the comea was covered by a conjunctival flap. The children have been followed for one year and the condition is essentially unchanged.
Fig. 1. Family tree showing consanguinous marriage of the parents of the two patients.
The corneal button showed the characteristic features of pathologic corneal thickening. The basal epithelial cells exhibited hydropic swelling (HS). Numerous vesicular water clefts (subepithelial bullae, SB) were present in the superficial stroma (Fig. 4).
Case III: A male child aged 3 years was brought to the ophthalmic clinic with the complaint of increasing opacification of both cornea since birth. There was no history of photophobia. The parents were not related to each other before marriage. The general physical examination did not reveal any abnormality.
Ocular examination revealed uniform haziness of the cornea in both eyes without any vascularization (Fig. 3). The corneal epithelium was thickened and irregular. The anterior chamber and pupil were normal. The intraocular pressure was normal. The patient retained a visual acuity of 6/60 in each eye.
The diagnosis of congenital hereditary corneal dystrophy remained problematical until its true clinical character was determined by Franceschetti and Babel in 1945 as bilateral, symmetrical, and present at birth. With this defect, the cornea is diffusely cloudy and, in general, denser in the axial region and in the superficial layers of stroma. In a proportion of patients, the epithelium is edematous and occasionally the vision is comparatively little affected.
Most of the early authors classified this disease as congenital syphilitic interstitial keratitis, congential glaucoma, classical forms of hereditary dystrophy, or changes due to abnormalities of metabolism such as in Hurler's disease. Due to an erroneous diagnosis of buphthalmos, a fair number of such patients had to undergo surgical filtering operation. Further attention toward this congenital dystrophy was drawn by Maumenee who discussed 12 patients with this condition.2 Keates and Cvinthal3 observed the presence of this disease in three males among nine siblings.
The diagnosis for the three patients described in this report was congenital hereditary corneal dystrophy (two patients belonged to the same family) and conformed well to the classical picture. The clinical picture was characterized by diffuse corneal opacity of a ground-glass type, first noted at birth or soon after. The corneal epithelium is frequently bedewed or roughened so that it has a pigskin appearance, but bullae are rarely seen. The eyes are not photophobie or inflamed. In the present patients, the stroma was thickened and diffusely edematous, but it had remained avascular. The corneal diameter and intraocular pressures in all remained normal and there was no damage to the optic-nerve head. None of the patients showed mental deficiency, chondrodystropic skeletal changes, dwarfism, or hepatosplenomegaly. Urine mucopolysaccharide tests were normal, and excluded Hurler's disease. Histopathological studies of a corneal button from one of the present patients show that the main pathological defect is a diffuse edema of the corneal stroma. The hydropic swelling of the basal layer of the epithelial cells and highly irregular thickening of Bowman's membrane (Fig. 4) are important changes and are considered to be secondary to stromal edema.
Franceschetti, Klein, Forin, and Babel, commenting on the classification of congenital hereditary corneal dystrophy, grouped it as primary parenchymatous type of corneal dystrophy.6 Maumenee, however, speculated that the possible mechanism for the abnormal corneal hydration might result either from abnormal embryonic development of the stroma itself or from a congenital form of endothelial dystrophy.2 Abnormalities of the stromal mucopolysaccharide composition7 and premature maturation of the corneal development might have a significant role in corneal hydration. Electron-microscopic study of the corneal button from such a patient showed that Descemet's membrane was thin and irregular which was highly suggestive that a functionally normal endothelium could not have been present during the embryonic period.4
Fig. 2. Case I: Ground-glass appearance of cornea in both eves.
Fig. 3. Case 3: Showing corneal haziness on both sides.
Fig. 4. Light micrograph of epithelium and superficial stroma from Case I, showing thickening of epithelium and hydropic swelling (HS) of the basal epithelial cells. (Haematoxylin-Eosin., x i40).
Three patients with congenital hereditary corneal dystrophy with histological changes are described. The condition has to be differentiated from other diseases which produce congenital haziness of the cornea.
Acknowledgments: The authors wish to thank Dr. M. Balasubramanyan, M.D., Principal, JIPMER, for according permission to publish the material. Thanks are also due to Dr. (Mrs) Kamla Chandra, Professor of Pathology, for the histopathological comments.
1. Franceschetti, A. and Babel, J.: Anatomical Classification of Familial Degenerations of Cornea. Ophthalmologica, 109? 169, 1945.
2. Maumenee, A. E.: Congenital Hereditary Comeal Dystrophy. Amer J Ophth, 50: 114, 1960.
3. Keates, R.H. and Cvintal, T.: Congenital Hereditary Corneal Dystrophy. Amer J Ophth, 60:892, 1965.
4. Kenyon, K. P. and Maumenee, A. E.: Invest Ophth, 7: 475-500, 1968.
5. Pearce, W. G.; Tripathi, R. C.; and Morgan, G.: Congenital Endothelial Comeal DystrophyClinical, Pathological, and Genetic Study. Brit J Ophthal, 53: 577, 1969.
6. Franceschetti, A.; Klein, D.; Form, S.; and Babel, J.: Clinical and Social Aspects of Hereditary in Ophthalmology. XV Int Cong Ophth, 1:157, 1950.
7. Hedbys, B. O.: The Role of Polysaccharides in Comeal Swellings. Expt Eye Res, 1: 81, 1961.