Transcript
Page 1: CORNEAL THICKNESS AND ENDOTHELIAL DAMAGE AFTER INTRAOCULAR LENS IMPLANTATION

A C T A O P H T H A L M O L O G I C A V O L . 5 8 1980

Department of Ophthalmology (Head: N . Ehlers), hhus Kommunehospital, University of Aarhus and

Department of Ophthalmology (Head: E . Westerlund), Central Hospital, NykQbing Falster, Denmark

CORNEAL THICKNESS AND ENDOTHELIAL DAMAGE AFTER INTRAOCULAR LENS IMPLANTATION

THOMAS OLSEN and JENS SINDBERG ERIKSEN

The corneal thickness and the specular appearance of the corneal endothelium are reported in 100 patients with unilateral intraocular lens implantation. Post-operative time ranged from one to 42 months. An average central endothelial cell loss of uncomplicated cases of 46%, range 1 to 83%, with no correlation with time after the operation was found. A significantly higher cell loss was found in cases with technical complications, shallow anterior chamber or increased intraocular pressure post-operatively. No correlation was found between the corneal thickness and the endothelial cell loss. In two patients, however, with a cell density below 500 cells/mm*, a slight increase in corneal thickness was noted. Thirty patients presented a guttate endothelium. Ir- respective of the occurrence of surgical complications the presence of a guttate endothelium was found to be a major determinant of the corneal thickness increase and could be ascribed as a cause of persistent corneal swelling in six of twelve patients with elevated corneal thickness. The progression of guttate changes occurred independently of the cell loss.

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

Cataract extraction combined with an intraocular lens implantation is now be- coming an increasingly employed surgical procedure. Along with the good refrac- tive correction it provides to the patient, this insertion of a foreign body into the eye has its costs, however. One of the feared complications is persistent corneal oedema, which seems to occur more frequently after lens implantation than after simple cataract extraction (Jardine & Sandford-Smith 1974; Pearce 1972, 1975; Duffner

Received March 10, 1980.

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Thomm Olsen and Jens Sandberg Eriksen

et al. 1976; Baggesen et al. 1978). The incidence of corneal oedema reported in these studies ranges from a few per cent to 13%. Other investigators have failed to demonstrate this higher incidence (Binkhorst & Leonard 1967).

In recent years a number of specular microscopic studies have reported a greater endothelial cell loss associated with lens implantation than without lens implantation after cataract extraction (Bourne & Kaufman 1976; Forstot et al. 1977; Cheng et al. 1977; Sugar 1979; Abbott & Forster 1979; Galin et a]. 1979). Some authors have not found this higher cell loss (Hirst et al. 1977; Binkhorst et al. 1978). In these studies the cell loss after lens implantation ranges from 7 to 62%. The post- operative follow-up time, however, also varies considerably. Because a redistribu- tion of the cell population occurs during the first months after the operation (Rao et al. 1978; Sugar 1979; Galin et al. 1979) this makes a direct comparison of the studies difficult. The lowering of the cell population has been viewed with some concern because a low cell density presumably renders the cornea more susceptible to the development of corneal oedema (Irvine 1956; Capella 1971; Stocker 1971; Bourne & Kaufman 1976a; Kaufman 1979).

The immediate post-operative increase in corneal thickness after lens implanta- tion seems to be higher than after simple cataract extraction (Cheng et al. 1977a; Praeger & Schneider 1977). Because of the quantitative association between cell loss and immediate corneal thickness increase after cataract extraction (Olsen 1980), this is to be expected. In the above mentioned studies, however, corneal thickness was found to return to normal levels some months after the operation. It is remarkable, that even in case of very high immediate increase in corneal thickness after surgery, and therefore presumably a high concomitant cell loss, the ultimate thickness has been reported to return to its pre-operative level (Giardini & Cambiaggi 1956). It therefore seems that the long-term effect of endothelial cell loss on the corneal thickness still remains to be shown.

The present investigation was undertaken in order to elucidate the role of the endothelium for the ultimate hydration of the cornea after cataract extraction with lens implantation. By this study it was attempted to throw light upon the still unsettled question of the information yielded by the endothelial reflex and its significance for corneal hydration.

Subjects and Methods At the Central Hospital in Nykebing Falster cataract extraction with lens implantation has been employed since 1976 in patients with senile cataract and more than 60 years of age. Indication for lens implantation has generally been found if the patient presented with no history of uveitis, no present eye inflammation, corneal oedema or marked endothelial dystrophy, glaucoma, retinal detachment, juvenile onset diabetes, myopia > 7 dioptres or a shallow anterior chamber.

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Intraocular Lens Implantation

The surgical procedure was intracapsular cryoextraction with corneal incision. Pre-opera- ive treatment consisted in diamox 500 mg intravenously and eye ball massage. The lens used hroughout was a Federow iris clip lens (manufacturer: 3M). No special lens coating solution vas used to lubricate the lens prior to insertion. To obtain fixation of the lens dry pilocarpine vas applied to the wound edge. Normal saline was used as irrigating solution if necessary. Mound closure was done with 8-0 running Dexona or Vicryla absorbable suture. All but a ew operations were done by one surgeon (E.W.). Post-operatively, the patients were treated vith pilocarpine eye drops and prednisolone ointments for six and one months, respectively.

For the present study only patients with an unoperated fellow eye without previous trauma ir disease other than cataract were included. In this way 140 patients with unilateral lens mplant were selected from the operated series. Eighteen patients had died since the )peration. Nine patients could not be traced or did not show up for the present follow-up nvestigation. Seven patients were omitted due to poor general condition. Four patients had he pseudophakos removed shortly after surgery due to dislocation of the lens and were .xcluded from the study.

At the present follow-up examination corneal thickness measurements were deferred (and pecular microscopic examination not attempted) in two patients with clear corneas due to nability of the patients to fixate a target. One patient presented with an iridocyclitis on the )perated side. Because none of the other patients showed this complication this patient was kxcluded from the below grouped data (the corneal thickness was 0.550 and 0.5 10 mm of )perated and unoperated side, respectively, and the cell loss was 46% on the operated side).

This leaves 99 patients, 39 men and 60 women, in the age range from 62 to 91 years, with a inilateral lens implant. Of these, two patients had previously undergone intracapsular .ataract extraction, whereas the rest of the patients had no previous history of disease or rauma in the now pseudophakic eye. The time period from the operation to the present 'xamination ranged from one to 42 months.

Data concerning complications that occurred during or after the operation were obtained Ptrospectively from the case record.

Central corneal thickness was measured with a modified Haag-Streit pachometer (Ehlers & iperling 1977). Each measurement was taken as the closest 5 pm reading on the scale reading )f the pachometer. Single determinations were used, the standard deviation of which has Ieen found to be 5-6 pm from a large number of readings on several individuals. Corneal hickness of non-operated eye was taken as control. In what follows residual corneal thickness ncrease refers to central corneal thickness of operated eye minus thickness of non-operated :ye.

The corneal endothelium was photographed with a non-contact specular microscope Olsen 1979) in a central area of both sides, and 2-3 mm superiorly in the operated eye. If he specular photomicrographs from the central endothelium revealed one or more circular lefects in the endothelial reflex larger than two cells width, the endothelium was classified as 1 guttate endothelium. By using contralateral eye as control a cell loss was estimated as the 3ercentual decrease in cell count from unoperated eye.

Resu I ts >orneal thickness

rhirty patients showed a guttate endothelium with bilateral involvement in 28 of he cases. Irrespective of the occurrence of surgical complications the presence of a

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Thomas OLren and Jens Sindberg Eriksen

guttate endothelium was found to be an important factor for the residual thickness. As shown in Table I the guttate changes were wOrse (more numerous and larger defects in the endothelial reflex) in the operated eye in about two-thirds of the cases which were largely responsible for the increased thickness in this group.

In order to further analyse possible factors influencing the corneal hydration the patients were grouped as shown in Table 11. If per-operative complications such as excessive vitreous loss or difficulty in lens placement had occurred, or a dislocation of the lens had occurred post-operatively, the patients were classified as technical complications. The mean side difference in corneal thickness for this group was not different from the group of uncomplicated cases without guttate endothelium.

Fourteen patients had a shallow anterior chamber post-operatively. The inter-eye difference of this group differed significantly from the reference group (Table I). Six of the patients, however, also had endothelial guttae, and when these subjects were withdrawn the mean side-difference diminished to 0.007 (+ 0.020) mm, not different from the reference group.

The group with increased intraocular tension comprised patients with medica- mentally treated ocular hypertension and patients with a tension higher than 22 mmHg found at the present follow-up examination. Although this group showed the highest mean side difference in corneal thickness, the scatter was large and the P-value just about the five per cent level. Two patients in this group had endothelial

Table I. Bilateral comparison of endothelial dystrophy and corneal thickness in

30 patients with unilateral lens implant.

I I ACCT Specular microscopic appearance 1 1 RTSD)

Worse in operated eye 21

Similar involvement on both sides 8

+ 0.035” (i 0.039)

+ 0.003 (+ 0,012)

Worse in non-operated eye 1 - 0.01

Total + 0.025

(T 0.036) 30

ACCT = central corneal thickness of operated eye minus thickness of non-operated eye (mm).

P < 0.01 by Mann-Whitney U-test, compared to second group listed.

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Tabl

e 11

. C

entr

al c

orne

al th

ickn

ess (

CC

T) (

mm

) in

99 p

atie

nts

with

uni

late

ral l

ens i

mpl

ant.

(mea

ns T

SD

).

Uno

pera

ted

Ope

rate

d M

ann-

Whi

tney

U

-tes

t**

Dif

fere

nce

No

surg

ical

co

mpl

icat

ions

0.52

7 0.

532”

+

0.00

5 (T

0.0

26)

(T 0

.029

) (T

0.0

14)

49

- g

utta

te

endo

thel

ium

+ gut

tate

en

doth

eliu

m

18

0.54

0 (i

0.02

7)

0.56

4 (i

0.04

3)

+ 0.

024

(T 0

.041

) P

< 0.

05

Tec

hnic

al co

mpl

icat

ions

.l

0.55

2 +

0.01

1 (T

0.0

15)

(7 0

.024

) (T

0.0

12)

n.s.

0.

541

10

Shal

low

ant

erio

r cha

mbe

r 0.

520

0.53

2 14

(T

0.0

20)

(T 0

.029

) +

0.02

2 (T

0.0

31)

P <

0.0

5

~

Intr

aocu

lar

pres

sure

>

22 m

mH

g po

st-o

pera

tivel

y

~ ~

~~

~~~~

~ _

__

~

~

+ 0.

038

(T 0

.026

) (T

0.0

82)

(T 0

.067

) P - 0

.05

0.52

3 0.

56 1

10

Tot

al

0.53

0 0.

544

+ 0.

014

(T 0

.026

) (T

0.0

41)

(T 0

.033

) 99

*=

indi

cate

s sig

nifi

cant

(P <

0.05

) dif

fere

nce

by S

tude

nt’s

pai

red

t-te

st.

** T

he

mea

n C

CT

dif

fere

nce

was

test

ed a

gain

st m

ean

diff

eren

ce o

f the

firs

t gro

up li

sted

. **

(*( T

wo

patie

nts

fell

into

two

grou

ps:

One

pat

ient

had

lens

dis

loca

tion

and

a sh

allo

w an

teri

or c

ham

ber,

one

pat

ient

had

lens

dis

loca

tion

and

incr

ease

d in

trao

cula

r ten

sion

.

Page 6: CORNEAL THICKNESS AND ENDOTHELIAL DAMAGE AFTER INTRAOCULAR LENS IMPLANTATION

Thomas Olsen and /ens Sindberg Eriksen

+ 0.03 -

+ 0.01 - 0 -

- 0.01 -

A C C T M M

> 0.10 00

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 0 . 0

o m 0 0 co 00 0 0 0- 000 0

000 0 0 . 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 . 0 0

0 0 3 0 0 0 0 0 0 0 0 0 000 0000 0 0 0 0 00 0

co 0 00 00 00 0 0

0 0

0 0

0 0

+ 0.07

+ 0.05 I 0 0

dystrophy which, however, was of similar appearance on the two sides, their mean difference in corneal thickness being only 0.005 mm.

No significant change in corneal thickness with time after the operation was found in the present series (Fig. 1). When a group of patients with no surgical complications and without endothelial guttae was selected from the time period beyond six months, the mean residual corneal thickness increase was found to be + 0.005 mm (+ 0.015, (sD), n = 42) which was significantly different from zero, but not different from similar patients with shorter lens wearing time. Taking the group of patients free of complications and endothelial dystrophy as a reference group, the ‘normal’ values for residual thickness increase could be said to fall below 0.035 mm (= mean value plus two standard deviations) (dotted line in Fig. 1 ) . In this way 11 of the patients could be said to have abnormal persistent swelling of the cornea, with a central corneal thickness ranging from 0.545 to 0.760 mm of operated eye, 0.040 to 0.200 mm different from non-operated eye.

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Tabl

e III

. C

entr

al e

ndot

helia

l cel

l den

sity

(cel

ls/m

m*)

in 9

1 pa

tient

s w

ith u

nila

tera

l len

s im

plan

t. (m

eans

7 SD).

~ ~~

Unp

aire

d t-

test

C

ell l

oss

Uno

pera

ted

Ope

rate

d

2586

14

22

- 4

4.9

(T 3

62)

(T 5

39)

(i

19.3

) 49

- g

utta

te

endo

thel

ium

+ gu

ttate

en

doth

eliu

m

No

surg

ical

co

mpl

icat

ions

P

> 0

.60”

25

60

1326

- 4

8.1

(T 3

88)

(i

630)

(i

21.5

) 14

Tec

hnic

al c

ompl

icat

ions

10

23

84

(T 4

79)

101

1 (i

376)

- 5

7.7

(T 1

2.6)

P

< 0.

05””

Shal

low

ant

erio

r cha

mbe

r 12

25

8 1

(7 4

19)

942

(T 3

92)

- 6

3.5

(T 1

4.4)

P

< 0.

01””

P <

0.05

””

256

1 95

4 - 6

2.7

(7 4

01)

(T 4

42)

(7 15

.8)

8 ln

trao

cula

r pre

ssur

e >

22 m

mH

g po

st-o

pera

tivel

y

Tot

al

2552

12

68

- 5

0.3

(7 3

87)

(T 5

45)

(T 1

9.3)

91

”””

‘F M

ean

cell

loss

com

pare

d w

ith fi

rst g

roup

list

ed.

*” C

ell l

oss c

ompa

red

with

the

two

firs

t gro

ups c

ombi

ned.

*;

“” Tw

o pa

tient

s fe

ll in

to tw

o gr

oups

: One

pat

ient

had

lens

dis

loca

tion

and

a sh

allo

w a

nter

ior

cham

ber,

one

pat

ient

had

lens

dis

loca

tion

and

incr

ease

d in

trao

cula

r ten

sion

.

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Thomas Oken and Jens Sindberg Eriksen

Fig. 2 Central corneal endothelium in five patients with unilateral lens implant. Left part of figure: non-operated eye; right part: operated eye. Two patients at bottom of figure present a bilateral guttate endothelium with dominant appearance on the operated side. Bar = 100 pm.

Cell loss

In Table I11 the data on central endothelial cell densities have been grouped in the same way as in Table 11. In eight of the patients bilateral endothelial counts were not available due to poor quality of the photographs (l), extensive dystrophic changes of the endothelium or marked corneal oedema (7) (see Fig. 2). In the group with no surgical complications identical ‘unoperated’ cell counts were found

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Intraocular Lens Implantation

8 0 -

6 0 -

40-

2 0 -

in those patients with or without guttate endothelium. Since the central cell loss also did not differ, these two groups were pooled and compared to the group with complications. These groups of technical complications, shallow anterior chamber and increased intraocular pressure all had a significantly higher cell loss than the total group of uncomplicated cases. Irrespective of the occurrence of complications the mean cell loss of those with or without progression of dystrophic changes was 5 1.3% (n = 15) and 53.4% (n = 9), respectively (non significant).

In Fig. 3 the central cell loss of uncomplicated cases has been plotted against time after the operation. No significant relation was found. The vertical difference in cell density, i.e. the difference between superior and central counts, was also not significantly related to the post-operative time (r = -0.21, P > 0.05). The highest values (about 60% lower density in the superior region) were, however, found during the first four months. The mean decrease in cell count from the central area to the region 2-3 mm superiorly was 24% (+ 20) of uncomplicated cases. No correlation was found to the age of the patient in the present series (r = 0.19, P > 0.05). A somewhat higher difference in vertical density was found in those patients with a guttate endothelium (33.4% vs. 21.5% lower cell count in the superior region for uncomplicated cases with and without dystrophy, respectively, (P = 0.07).

0 0

* o 0 0 0

Correlation between cell loss and corneal thickness

No correlation was found between endothelial cell density and corneal thickness of unoperated eye (r = 0.12, P > 0.05, n = 98). No correlation was found between the

C E L L LOSS

%

0

*O

.go 0O0

00

0

o o 0 00°

80 0 0

0 0

000 0

0

0 0 0

0

0 0

0

0 10 0 5 10 15 2 0 2 5 30 35 40 M O N T H S

Fig. 3 . Central endothelial cell loss of uncomplicated cases related to time after lens implantation.

Meaning of filled and open circles explained in Fig. 1.

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Thomay Olsen and Jens Sindberg Eriksen

+ 0 . 0 7 -

i 0 .05 -

+ 0.03-

+ 0.01 -

A C C T

I M M

1 + 0.07

+ 0.05 lo + 0.03

i 0.01

- 0.01 O I

0

0

a o a 0.

. o 0 0 0 . -0

05. 0 o o a m o 005 000 a30 0 0

0 o o [ ) c o c o o 0 a300 03.0

00 0 005 0 00

0

0

am am

05 0 0 0

0 0 0

0 000

0

r 0 10 2 0 30 40 5 0 60 7 0 8 0 % C E L L LOSS

Fig. 4. Percentual difference in central endothelial cell count (‘cell loss’) related to difference in central corneal thickness (ACCT) between operated and non-operated side in 91 patients

with unilateral lens implant. Meaning of filled and open circles explained i Fig. 1. (r = 0.13,P = 0.2).

A CCT

I M M

- 0.01 “1

0

0 . 0

0 0

0 0 e. 0 0 0

0 0 0

0

0 0 0 0 0 0 0

0 0 0 0

0 r 0 200 400 600 800 ‘ 1 , b O CELLS/MM2

Fig. 5. Correlation between residual corneal thickness increase and endothelial cell density of operated eye for cell densities below 1000 cells/mm2. Meaning of filled and open circles

explained in Fig. 1. (r = -0.33, P = 0.09).

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Intruoculur Lens Implantation

cell loss and residual corneal thickness (Fig. 4). Considering only very low cell densities, no significant relationship was found either (Fig. 5). However, when the individual points are considered in Fig. 5, it is seen that two points with a cell density below 500 cells/mm2 fell above 0.035 mm, the aforementioned upper ‘normal’ limit of the residual corneal thickness. One of these patients (cell density 286 cells/mm2) had previously undergone an intracapsular cataract extraction. After the secondary lens implantation she had a short period with a shallow anterior chamber and lens-cornea contact. The operative course of the other patient was uneventful. None of them had endothelial dystrophy or abnormal intraocular pressure.

Discussion

In the present study, the most important factor found to influence the corneal thickness after lens implantation was the presence of a guttate endothelium. Progression of dystrophic changes could be said to be the main factor responsible for persistent corneal swelling in six of the eleven patients with abnormal hydration depicted in Fig. I. In the remaining five patients other factors had to be sought.

A remarkable result was that no significant correlation could be established between the endothelial cell loss and the residual corneal thickness increase. For cell losses up to more than 80% or cell densities down to 500 cells/mm2 there seemed to be absolutely no association between cell count and corneal thickness. In two patients, however, with a cell density below 500 cells/mm2 the cornea was somewhat thicker on the operated side. It cannot be excluded that these two patients thus had a borderline function of the endothelium due to an inadequate number of cells.

Considerations on the prevalence of a ‘low cell density syndrome’ have to be made with due regard being paid to those corneas in which marked oedema hinders a specular microscopic examination. In two patients with normal endothelium on the non-operated side the endothelium could not be studied due to severe oedema. The oedema in these patients had developed in parallel to the development of ocular hypertension. As indicated in Table 111, an increased post-operative intraocular pressure may add to the endothelial cell loss associated with the operation. It is therefore possible that in these two cases the intraocular pressure had caused a further irreversible damage to the endothelium with corneal oedema as a result. In one patient (residual thickness increase 0.04 mm) neither dystrophy, low cell density, or inflammation could be associated with the corneal swelling, the cause of which thus remained uncertain.

The majority of the patients showed a corneal thickness on the operated side which was close to that of the non-operated side. The mean residual thickness

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Thomas OOen and Jens Sindberg Eriksen

increase of uncomplicated cases without dystrophy of 5 pm, although statistically significant, is clinically an insignificant swelling and did not change with time. The cause of this swelling remains unknown. A swelling of the same small magnitude has been found six months after intracapsular cataract extraction with a cell loss half of that found in the present study (Olsen 1980).

The higher cell loss in the present study is strongly suggestive of a higher immediate post-operative corneal thickness. While performing the present investi- gation the corneal thickness of one patient was measured before and the first day after lens implantation. An increase of 0.2 mm was found after an uneventful operation. This is close to the double of the mean increase found in the above mentioned study.

The cause of the high cell loss associated with lens implantation needs some consideration. Contact between the lens and the endothelium is one important factor (Kaufman et al. 1977). The use of an air interface between the cornea and the lens during the operation has been shown to reduce the cell loss (Bourne et al. 1979). The duration of the operation is longer with lens implantation, and during that time the endothelium is deprived a normal nutritive supply from the aqueous humour. The composition of the irrigating solution may be of particular signifi- cance. Calcium has been shown to be necessary for the integrity of the endothelium (Kaye et al. 1968), and a Ringer solution or other enriched solutions cause less damage to the endothelium than normal saline (Edelhauser et al. 1975).

What ever the nature of the technical improvements by which the endothelial damage can be reduced, the present study demonstrates that the patient is a factor per se which must not be neglected. One such risk factor is the presence of a guttate endothelium. It is remarkable that the progression of dystrophic endothelial changes occurred independently of the cell density and the surgical cell loss. The provocative factor which caused the progression of the dystrophy therefore remains speculative.

Acknowledgments

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

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Intraocular Lens Implantation

Ref ere n ces

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Baggesen L. H., Land A. M. & Nielsen N. V. (1978) Results from lens implantation. A material from Danish hospitals. Acta ophthal. (Kbh.) 56, 4 14-42 1.

Binkhorst C. D. & Leonard P. A. M. ( 1967) Iris-clip pseudophakos implantation. Amer. J . Ophthal. 64, 947-956.

Binkhorst C. D., Nygaard P. & Loones L. H. (1978) Specular microscopy of the corneal endothelium and lens implant surgery. Amer. J . Ophthal. 85, 597-605.

Bourne W. M. & Kaufman H. E. (1976) Endothelial damage associated with intraocular lenses. Amer. J . Ophthal. 81,482-485.

Bourne W. M. & Kaufman H. E. (1976a) Cataract extraction and the corneal endothelium. Amer. J . Ophthal. 82,44-47.

Bourne W. M., Bruhaker R. F. & OFallon M. (1979) Use of air to decrease endothelial cell loss during intraocular lens implantation. Arch. Ophthal. (Chicago) 97, 1473- 1475.

CapellaJ. A. (1971) T h e pathology of corneal endothelium. Ann. Ophthal. 3, 397-400. Cheng H., James A. & Rubinstein B. (1977) Corneal edema - iris-clip implantation and simple

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Duffner L. R., Wallace K. W. & Stiles W. R. (1976) Copeland intraocular lens. Amer. J . Ophthal. 82, 590-593.

Edelhauser H. F., Van Horn D. L., Hyndiuk R. A. & Schultz R. 0. (1975) Intraocular irrigating solutions. Their effect on the corneal endothelium. Arch. Ophthal. (Chicago) 93,

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Forstot S. L., Backwell W. L., Jaffe N. S. & Kaufman H. E. (1977) The effect of intraocular lens implantation on the corneal endothelium. Trans. Amer. Acud. Ophthal. Otolaryngol. 83,

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Giardini A. & Cambiaggi A. (1956) Recherches sur I’epaisseur corneenne apr& extraction d e

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