A C T A O P H T H A L M O L O G I C A V O L . 5 8 1 9 8 0

Department of Ophthalmology (Head: N . EhlerA), University of Aarhus, DK-8000 Arhus C, Denmark

CHANGES IN THE CORNEAL ENDOTHELIUM AFTER ACUTE ANTERIOR UVElTlS

AS SEEN WITH THE SPECULAR MICROSCOPE

BY

THOMAS OLSEN

I n order to investigate whether inflammation of the anterior uveal tract is accompanied by a loss of endothelial cells, 13 patients with previous unilateral attacks of anterior uveitis were photographed with the non-contact specular microscope. All patients had shown an increased thickness or frank oedema of the cornea during the acute phase of the inflammation. As compared to the healthy eye, only two patients (15%) showed endothelial cell densities on the affected side which were lower than was to be expected from the normal difference between counts from left and right eye in a control population of 36 subjects. T h e two patients with detectable cell Ioss also showed defects in the specular reflex, the significance of which is discussed.

Key words: cornea - endothelium - non-contact - specular microscopy - uveitis.

Inflammation of the uveal tract is well known to have concomitant effects on the cornea. In acute anterior uveitis the corneal thickness increases (Mishima 1968; Polak 1969; Capella & Waltman 1971), and, following the acute attack, changes in the specular reflex of the endothelium have been described (Vogt 1930).

The increase in corneal thickness associated with the acute inflammation suggests that the barrier function of the endothelium is temporarily disturbed and raises the question of whether this is due to a loss of cells.

Due to the limited proliferative power of the adult human endothelium (Kauf- man et al. 1966; Stocker 1971) and the high concordance between cell densities from right and left eyes in normal eyes (Sturrock et al. 1978; Olsen 1979) a possible

Received August 10, 1979.

250

Cornraf endothelium and [interior uwiti7

Patient No.

unilateral cell loss can be assessed retrospectively by using the contralateral eye as a control.

Recently, a low endothelial cell density has been reported in some patients with iridocyclitis (Setala 1979).

Cell density (cells/mm2) CCT (mm)

Age Normal eye Affected eye Normal eye Affected eye

Subjects and Methods

Thirteen patients were included in the study. They comprised all patients who had been admitted to the eye clinic for the past one and a half years with one to several attacks of acute unilateral uveitis. Mean age was 40.2 years, range 23-69 years. With the exception of two patients who showed a weak seroreaction for toxoplasmosis no underlying etiology to the uveitis was found in any of the patients. In three patients the anterior uveitis coexisted with a posterior uveitis. During admission all patients were noted to have increased thickness or frank oedema of the cornea, and precipitates were found on the posterior aspect of the cornea. Patients were not classified according to the type of the precipitates. At the time of discharge, one patient had elevated intraocular pressure on the affected side while the remainder of the patients had normal pressures (appl.).

The shortest time period between discharge from the hospital and the present examination was three months (range 3-18 months). With the exception of three patients who showed a

Table I Cell density and central corneal thickness (CCT) in 13 patients with previous unilateral acute

anterior uveitis.

*) healed corneal ulcer on that side. **) faint aqueous flare on that side.

25 1

Thomnr Oltrn

faint aqueous flare on the affected side, no signs of acute inflammation were present at the time of specular microscopic examination and all the affected corneas (6 left and 7 right) were clear. N o medication was taken. The fellow eye had no history of disease or trauma and showed no signs of present disease.

The control group comprised 36 normal subjects in the age range 20-59 years (mean 34.0 years) with no history of eye disease or trauma other than squint or lens opacities. These subjects had been included in the normal series previously reported (Olsen 1979).

Both eyes of patients and normal subjects were photographed and central endothelial cell densities estimated as described earlier (Olsen 1979). From the control group a normal relative inter-eye variation in cell density was constructed by randomly choosing right or left eye as reference for the right-left difference in cell counts. By doing this, the small systematical right-left difference in normal eyes (Olsen 1979) is neglected. In the uveitis group. the difference in cell counts between the affected and the unaffected eye was expressed as relative to the unaffected eye.

Corneal thickness was measured as single determinations using a modified Haag-Streit pachometer (Ehlers & Sperling 1977). The normal right-left difference in corneal thickness was based on bilateral measurements in 47 normal subjects with no history of eye disease or trauma other than squint or senile lens opacities. Age range of this group was 23-80 years with a mean of 59 years. Confidence limits were calculated on basis of the t-distribution.

Results

Crude data on the endothelial cell density and the corneal thickness in the patients at time of specular examination appear from Table I. In order to illustrate whether the cell count on the affected side was lower than should be expected, the relative difference in the uveitis group has been compared to the relative inter-eye difference in the normal group (Fig. 1). Standard deviation of the normal difference was found to be 4.4% which means that 95% of the normal inter-eye differences in cell counts are less than 8.9%, following the procedure of randomly choosing right or left eye as reference value. It is seen that only two of the thirteen uveitis patients (Nos. 8 and 10 in Table I) showed a difference which was larger than normal. One of these patients, a 49-year-old male, had had recurrent attacks of iridocyclitis complicated with moderately elevated intraocular pressure. In addition to the low cell count the endothelium on the affected side showed numerous defects in the specular reflex with a diameter below 50 pm (Fig. 2). The other patient, a 35-year-old female, had had two severe attacks of a combined anterior and posterior uveitis which had subsided without affecting the intraocular pressure. This patient also revealed numerous defects in the specular reflex on the affected side (Fig. 2). These defects were however large, 100-300 pm in diameter, almost circular and with sharply defined edges. Their size could not be brought to vary by altering the focusing depth or angle of slit illumination and cellular details were only scarcely visible within the defects. In the optical section with the ordinary

252

Corneal endothrliicm and nnterior uzleitzr

+ 15

+ 10

+ 5 .

0 -

- 5 -

- 10.

- 1 5

- 20

% A .

.

.

.. 9 ... ....................... a . . . . .

normal subjects

Fig. I

unilateral u veit is

The relative inter-eye difference in cell counts in 13 patients with previous unilateral anterior

uveitis (ordinate = affected eye-unaffected eye x 100%) as compared to the relative unaffected eye inter-eye difference in 36 normal subjects

x eye - contralateral eye contralateral eye (ordinate = x loo%, x denotes randomly chosen right or left eye.

slit lamp they were seen as old large sharply demarcated precipitates. Besides the occasional occurrence of scattered ‘physiological’ guttae none of the other patients showed this type of change in the specular reflex.

Central corneal thickness (CCT) was measured in both eyes of 47 normal subjects. 95% confidence limits for the normal difference between thickness of right and left eye (CCT left eye - CCT right eye) was -0.013 mm and +0.016 mm respectively. In practical terms this means that a difference of 0.02 mm or more is clearly abnormal. From Table I it is seen that three of the patients (Nos. 5 ,8 and 10) showed a CCT on the affected side which differed more than normal from the contralateral side. These patients also showed a faint aqueous flare on the affected side. In two of these patients a detectable cell loss had been found.

253

Thomas Olsen

Fzg. 2. The specular microscopic appearance of two corneal endothelia which showed a significant decrease in cell density following acute anterior uveitis. Top: guttae-like lesions in the endothelial reflex of a 49-year-old male with recurrent attacks of iridocyclitis. Buttom: large, circular ‘punched out’ lesions in the endothelial reflex of 35-year-old female with severe

attacks of panuveitis. Bar = 100pm.

Discussion

Since Leber’s time (1873) a destruction of the endothelium has been known to cause abnormal hydration of the cornea. The specular microscope enables this destruction to be quantitated if it has implied a loss of endothelial cells.

The patients included in this study have all had increased thickness or frank oedema of the cornea during the acute phase of their anterior uveitis. Only two patients (15%) showed a significant cell loss on the affected side. In these two patients at least part of the abnormal hydration of the cornea noted during the acute phase of the inflammation can thus be ascribed to a destruction of the endothelial cell layer. In the great majority of the patients however, no such cell destruction could be detected. Therefore in these patients, other factors have to be sought for the increased hydration of the cornea. Whatever the nature of such factors may be, the possibility remains that they may act by increasing the permeability of the endothelium without causing actual cell death.

254

Cor.nrrrl ~ndo thr l i i~m and cintrrior. uwiti,s

The patients with detectable cell loss in the present study also showed numerous defects in the endothelial reflex. One of these patients also had elevated intraocular pressure so that an effect of this on the appearance of the endothelium cannot be excluded (Setala & Vannas 1978). The other patient did not show this complication, and the observed defects were clearly different from ordinary guttae. Vogt (1930) described excrescences on the posterior aspect of cornea after inflammation as more irregular than ordinary guttae. The defects in the endothelial reflex seen in the present study were however large and almost circular giving an irregular outline only when they were confluent. In contrast to senile ‘physiological’ guttae the cellular outline of the endothelium lining the posterior aspect of these excrescenses could not readily be seen by altering the angle of illumination or focusing depth. The impression was that of a hyaline material deposited between the membrane of Descemet and the endothelial layer. In experimental uveitis inflammatory cells have been shown to enter this subendothelial space (Inomata & Smelser 1970). It is tempting to speculate that if the defects in the specular reflex seen in the present study constitute remnants of precipitates formed in the acute phase of the inflammation, they have gained access to the subendothelial space through a breakdown of the endothelial layer. Persisting ‘precipitates’ seen as defects in the specular reflex may thus be indicative of endothelial cell loss.

The two patients showing a decrease in the cell density on the affected side also had a thicker cornea on that side together with a faint aqueous flare. It is difficult to ascribe this minor increase in thickness to a relative decompensation of the endothelium as a result of damage in the acute phase or due to the still present inflammation in the eye. The one patient showing an increase in thickness without a decrease in cell density suggests the latter possibility.

Acknowledgments

This work was supported by the Danish Medical Research Council. The technical assistance of Mrs. Anette Poulsen is gratefully acknowledged.

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Thomus Olsen

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Author’s address:

Thomas Olsen, Department of Ophthalmology, Arhus Kommunehospital, DK-8000 Aarhus C, Denmark.