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 o f Ophthalmology (Head: N. Ehlers), h h u s Kommunehospital, University o f Aarhus, Arhus, Denmark

CORNEAL THICKNESS AND ENDOTHELIAL DAMAGE AFTER INTRACAPSULAR CATARACT EXTRACTION

THOMAS OLSEN

In a prospective study corneal thickness and specular microscopic findings of corneal endothelium are reported in 37 patients undergoing intracapsular cataract extraction. Central endothelial cell loss was estimated six months after the operation and was found to correlate significantly to the immediate post-operative increase in central corneal thickness. A subgroup of patients showing slight endothelial dystrophy prior to the operation showed a signifi- cantly higher increase in corneal thickness fourth day after the operation. Six months after the operation a significant residual increase in corneal thickness was found for this group, while the rest of the patients had returned to near pre-operative levels. No correlation was found between cell loss and residual corneal thickness increase at this time. Six months after the operation a vertical difference in cell density was found. This difference could be correlated to the age of the patient, presumably indicating a less complete redistribution of the cell population in older patients.

Key words: cataract extraction - cell loss - corneal thickness - endothelium - specular microscopy.

The damage exerted on the corneal endothelium during cataract extraction has been the subject of several specular microscopic studies (Bourne & Kaufman 1976; Cheng et al. 1977; Forstot et al. 1977; Hirst et al. 1977; Rao et al. 1978; Drews & Waltman 1978; Rao et al. 1979; Galin et al. 1979; Abbott & Forster 1979). A working hypothesis has been that the amount of the endothelial trauma, i.e. the cell loss is somehow related to the function of the endothelium and therefore to corneal hydration. The information yielded by the endothelial reflex on this respect is, however, still unsettled.

Received December 15th. 1979.

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Corneal thickne.n and endothelial damage

The post-operative endothelial cell density varies with time and location on the cornea. Evidence is now accumulating that the gradual decrease in cell density seen months after the operation (Hirst et al. 1977; Rao et al. 1978; Galin et al. 1979) is caused by a redistribution of the cell population (Rao et a1 1978; Sugar 1979), tending with time to even out imbalances in cell density created during surgery. This implies that a lowered central cell density is an inaccurate index of total cell loss in the early phases after the operation.

This study reports the immediate effect of endothelial damage on corneal thickness following intracapsular cataract extraction. In order to improve estima- tion of the cell loss, post-operative cell densities were not estimated until six months after surgery.

Subjects and Methods

A total of 45 subjects with senile cataract entered the study. This group comprised all patients consecutively admitted to the eye department during a two months period where indication for intracapsular cataract extraction was found. Patients with co-existing eye diseases such as glaucoma, uveitis or corneal diseases were excluded. Generally patients were not advocated surgery if endothelial dystrophy was revealed in routine slit lamp examination. Not seldomly, however, the specular microscopic examination revealed a guttate endothelium in the endothelial reflex which was not readily detected in ordinary slit lamp examination. In such cases surgery was not abandoned and the patients were included in the study.

T h e operational procedure was intracapsular cryoextraction with corneal incision and zonulysis. For irrigation a Ringer solution was used. The wound was closed with running 10-0 nylon suture. The operations were performed by a number of surgeons. No regard was paid to the particular surgeons experience. Occurrence of vitreous loss or other pre-operative complications did not exclude the patient from the series.

Prior to surgery the central endothelium of all patients were photographed with a non-contact specular microscope (Olsen 1979). The central corneal thickness was measured the day before and on each of four days after surgery using a modified Haag-Streit pachometer (Ehlers & Sperling 1977). All measurements were single determinations taken as the closest 5 I”. position on the scale reading of the pachometer, and were done by the author shortly after noon. The standard error of single determinations with the present method has repetitively been found to be 5-6 p (about l%), estimated from a large (>20) number of measurements of several subjects.

Six months after the operation the patients were asked to attend the clinic for reexamina- tion. The central endothelium was photographed as described above and in addition an area 2-3 mm superiorly to the center of the cornea was photographed by directing the gaze of contralateral eye. Again corneal thickness was measured. Intraocular pressure was measured with an applanation tonometer attached to the slit lamp. Seven patients did not show up for the reexamination. One patient was excluded because of post-operative glaucoma. Age range of the remaining patients, 16 men and 21 women, was 57-87 years with a mean of 73.6 years. These 37 patients are reported on in the following. Unless specified otherwise statistical analyses were based on distributional methods. For comparison of means Student’s t-test was employed.

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Results

Pre-operative and post-operative central cell density of operated eye was (mean f SD) : 254 1 (f 423) and 1894 (f 50 1) cells/mm*, respectively, with a mean cell loss of 25.1 (k 16.4) %. Pre-operative central corneal thickness of operated eye was 0.530 (k 0.03 1) mm. No correlation was found to pre-operative cell density (r = 0.16, P > 0.3). The immediate increase in central corneal thickness was 0.085 (+ 0.066), 0.073 (f 0.050), 0.059 (k 0.027) and 0.054 (k 0.028) mm the first, second, third and fourth day after the operation, respectively. For each day this increase was found to correlate significantly to the central cell loss (r = 0.73, 0.59, 0.56 and 0.58, P < 0.00 1, for day one through day four, respectively). The strongest correlation was thus found on the first post-operative day (Fig. 1). Dotted line in Fig. 1 indicates regression line y on x calculated using the method of least squares for thickness increases below 250 p. Intersection on ordinate is not significantly different from the origin.

Six of the patients turned out to have guttae in the endothelium as revealed on the pre-operative photographs of the central endothelium. These changes were

Central cell loss (%I 7c

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5c

4c

3c

2C

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. . .. .

. . . = ' . . . ., ' . . .. . . '

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JO 100 150 200 2 5 0 300 350 400

A CCT (Am) first day after operation Fzg. 1.

Correlation between first day post-operative increase in central corneal thickness (CCT) and central endothelial cell loss estimated six months after cataract extraction. Dotted line

indicates regression line y on x. (r = 0.73, P < 0.001).

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0 I I

A CCT I y m l

120 -

100 -

80 -

60 -

g u l l e l e endof hel ium

1 2 3 4 days 180

Fig. 2. Mean post-operative increase in central corneal thickness (CCT) in 31 patients with normal endothelium and 6 patients with minor dystrophic changes in the endothelium. Asterisks indicate significant (P < 0.05, by Student's t-test) difference among the groups on day four and persistent elevated thickness six months after surgery for the group with guttate

endothelium. Vertical bars indicate standard errors of the mean.

bilateral. Mean pre-operative corneal thickness of this group was 0.540 (+ 0.017) mm, not significantly different from the rest of the patients. The post-operative increase in corneal thickness for this group was larger than in the patients with normal endothelial reflex and became significantly different fourth day after the operation (Fig. 2). The mean cell loss of 29.7 (+ 20.1) 5% for this group was however not significantly different from the rest of the patients.

For the total group neither pre-operative cell density visible pleomorphology of the cells, pre-operative corneal thickness, age nor sex was significantly related to the thickness increase or central cell loss.

Six months after the operation central corneal thickness was almost normalized in the normal group. Mean residual thickness increase was 0.006 (+ 0.018) mm, not significantly different from zero. In the group of pre-operative indothelial guttae the residual thickness increase was 0.018 (+ 0.020) mm, which is close to, but significantly (P < 0.05) different from zero. In these patients the endothelial changes had worsened in all cases, that is, the defects in the endothelial reflex were larger and more numerous than before the operation (Fig. 3). No guttai-like changes were found in those eyes with previous normal endothelial reflex (Fig. 4).

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No correlation was found between cell loss and residual corneal thickness at this time in the entire group (r = 0.22, P > 0.1). All corneas were clear. Corneal thickness of unoperated eye showed a mean change of -0.001 (+ 0.012) and -0.003 (k 0.012) mm in the normal and guttae-group, respectively.

The superior counts found six months after the operation were as a group lower that the central counts. Mean decrease from central to superior counts was 18.8%, range -3 to +57%. This vertical difference in cell density was found to correlate significantly to the age of the patient (Fig. 5). For graphic simplicity the data have been pooled and averaged in three age groups. No difference was found between the vertical density difference in the guttae-group as compared to the normal group (mean values 26.5 (+ 18.5) %, n = 3 vs. 18.0 (+ 16.4) %, n = 29, respectively, P < 0.4). In five patients counts from the superior region were not available due to poor quality of photographs or extensive guttae-changes. No relation was found between the vertical density difference and residual corneal thickness increase six months after surgery.

Fig. 3. Central corneal endothelium before (top) and six months after (bottom) intracapsular ( ataract extraction in a seventy-one-year-old woman with guttate endothelium. The cell density has decreased 49% from 2480 to 1270 cells/mm*. Central corneal thickness increased

0.190 mm first day after the operation. Bar = 1 0 0 ~ .

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o - - - -

Fig. 4 . Central corneal endothelium before (top) and six months after (bottom) intracapsular cataract extraction in a sixty-nine-year-old woman. The cell density has decreased 37% from 2910 to 1820 cells/mm*. Central corneal thickness increased 0.190 rnm first day after the

operation. Bar = loop.

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Discussion

The mean cell loss reported after intracapsular cataract extraction ranges from 4 to 2 1 % (Bourne & Kaufman 1976; Cheng et al. 1977; Forstot et al. 1977; Hirst et al. 1977; Rao et al. 1978; Drews & Waltman 1978; Galin et al. 1979; Abbott & Forster 1979). In these studies the post-operative time until evaluation generally varies from a few days to several months. The mean cell loss of 25% found six months after the operation in the present study may seem higher than in the studies cited above. Some of this discrepancy undoubtly is accounted for by the longer post-operative period in the present study. Because of the sliding phenomenon central counts may be expected to indicate total cell loss better the longer the post-operative follow-up period. Galin et al. (1979) state that the post-operative decrease in central counts is minimal after three months. The still present vertical density difference found in the present study after six months (Fig. 5) indicates that a complete redistribution of the cell population has not taken place at this time, at least in the age range studied. Whether the central count after this time really reflects the mean decrease in cell density is unclear. To answer this, a complete mapping of the corneal endothelium post-operatively seems necessary.

Another factor which must be considered when comparing cell losses reported by different investigators is that only clear corneas can be studied. At the present follow-up examination all corneas were clear ensuring that no endothelial photo was excluded on the grounds of an oedematous cornea, a problem which may arise in the early post-operative days and especiallly in case of great cell loss.

The average increase in corneal thickness found in the present study in the early post-operative days seems to be in agreement with the results of Norn (1973), Wood & Maumenee (1975), and Bramsen et al. (1978). Somewhat greater thickness increase was found by Cheng et al. (1977). Giardini & Cambiaggi (1965), in a study of extra- and intra-capsular extractions, found an average of 45% increase in corneal thickness on third day after the operation. Presumably this high increase may be due to the different surgical technique employed twenty years ago (Norn 1973).

Most authors agree that the corneal thickness returns to normal less than six months after the operation (Cheng et al. 1977; Norn 1973; Wood & maumenee 1975) even in the case of very high immediate encrease (Giardini & Cambiaggi 1956). At variance is the finding of Miller & Dohlman (1970) who stated that 76% of 50 unilateral aphakic subjects more than six months after the operation still showed increased corneal thickness on the operated side. As was shown by Wood & Maumenee (1975), and as was the tendency in the present investigation, the ultimate thickness depends on the pre-operative condition of the endothelium. No

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Corneal thickness and rnrlothelial damage

information was given on the status of the endothelium in the series reported by Miller & Dohlman (1970).

The present investigation revealed a strong correlation between the immediate corneal thickness and the cell loss index, i.e. the central cell loss. Like the situation with estimates of the cell loss, central corneal thickness increase can only be regarded as an index of the total volumen change or water intake of the cornea. Whether the central increase represents the mean thickness is dependent on the fluid distribution within the cornea, which varies considerably with time and among different individuals (Giardini & Cambiaggi 1956). Generally, however, the cornea is thicker in the upper part and thinner in the lower part, with an intermediate thickness in the center. By expressing the cell loss as per cent of initial value, the relationship depicted in Fig. 1 is in fact a correlation between an index of the water intake of the cornea and an index of the area broken down of the endothelium as a result of the surgery. This relationship bears a remarkable resemblance to the situation in acute glaucoma (Olsen 1980).

The reason why other authors who have measured both the corneal thickness and the central cell loss did not find this close relationship may be found in the shorter post-operative period studied. Bourne & Kaufman (1976) noted however, that those corneas with ‘significant’ cell loss also had greater increase in thickness. Cheng et al. (1977) noted that cataract extraction with lens implantation gave more cell loss and greater increase in corneal thickness than without lens implantation. Experimentally, the quantitative correlation between damaged endothelial area and corneal thickness response has been demonstrated by Honegger (1962) and Van Horn et al. (1977).

It is noteworthy that the cell loss observed in the present study did not induce a permanent decrease in the deturgescence function of the cornea. Only those with pre-operative guttate endothelium had not returned to pre-operative corneal thickness after six months. It appears that the integrity of the normal endothelium althouth deprived up to 63% of its cells (found in the present study) alone can maintain normal corneal thickness, at least in the range of lowered cell densities observed in the present study. A similar observation has been made by Forstot et al. (1977) and in corneal grafts (Bourne & Kaufman 197th; Laing et al. 1976; Sato et al. 1978). Another remarkable result was that no newly formed guttae had developed as a result of the cell loss. This challenges the hypothesis held by Capella (1972) that the cell damage as such initiates the production of abnormal Descemet’s membrane material, and add some evidence against the view of Fuchs’ endothelial dystrophy being a low cell density syndrome (Olsen 1980).

It was surprising to find a persistent vertical difference in cell density six months after surgery. Whether this imbalance in cell density was a stable situation or a further reduction would occur with time is yet unclear. Apparantly the mobility of

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Thomas Olsen

the cells is dependent on the age of the patient as shown in Fig. 5 . T h e functional

significance of these findings remains unknown. It is hardly doubtful, however, that

if the cells were not able to move, there was n o way by which the endothelium could

reestablish an intact barrier function in response to injury.

Acknowledgments

This work was supported by grants from the Danish Medical Research Council and in part by the Danish Committee for Prevention of Blindness. The technical assistance of Mrs. Anette Poulsen is gratefully acknowledged.

References

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Author’s address: Thomas Olsen, M. D., Department of Ophthalmology, Arhus Kommunehospital, DK-8000 Arhus C, Denmark.

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