corneal metabolism and epithelial barrier function after cataract surgery and intraocular lens...

International Ophthalmology 19: 225-233, 1996. �9 1996 KIuwer Academic Publishers. Printed in the Netherlands.

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Corneal metabolism and epithelial barrier function after cataract surgery and intraocular lens implantation: a fluorophotometric study

A n n a M. L o h m a n n , Jaap A. van Best* & Ro b J.W. de K e i z e r Department of Ophthalmology, Leiden University Hospital, P.O. Box 9600, 2300 RC Leiden, The Netherlands (* corresponding author)

Accepted 3 January 1996

Key words: consensual reaction, corneal autofluorescence, corneal epithelial permeability, corneal metabolism, extracapsular lens extraction, fluorophotometry

Abstract

Purpose: The aim of this study was the assessment of possible changes in corneal metabolism and epithelial barrier function after an extracapsular lens extraction with artificial lens implantation. Methods: Ten patients without any eye medication were selected out of 140 patients attending for extracapsular lens extraction with lens implantation at the university hospital. Corneal metabolism was evaluated by fluorophotometric measurement of corneal autofluorescence. The corneal fluorescence values were corrected for interference by the fluorescence of the ocular lens. Corneal epithelial barrier function was evaluated by determination of corneal epithelial permeability. The permeability was calculated from the fluorescein penetration into the cornea after application of an eye bath containing fluorescein. Operated and fellow eyes were investigated 1 week before and 3-4 weeks after the operation. Results: The corneal autoftuorescence of the operated eye decreased significantly after surgery (mean decrease: 14%, Wilcoxon paired-sample test: P = 0.038). The corneal epithelial permeability of both eyes increased after surgery above the normal range of healthy controls (mean increase operated eye: 34%, P = 0.015, fellow eye: 32%, P = 0.15). Both corneal autofluorescence and epithelial permeability returned to normal values after one year. Conclusions: The lower corneal autofluorescence in the operated eye after surgery indicates a lower corneal metabolism which may be due to surgery. The increased epithelial permeability of both eyes implies a temporary impairment of the corneal barrier function. The interaction with the fellow eye indicates a consensual reaction which may attributed to damage to the neural system by the surgery.

Introduction

Extracapsular lens extraction (ECLE) has become a common operation in ophthalmology. Topical eye medication is necessary both before the operation, to obtain mydriasis during surgery, and thereafter to pre- vent inflammation and other complications resulting from the surgery. Intraocular penetration of topical eye medication takes place through the cornea after pass- ing the most important barrier for drugs, the corneal epithelium [1, 2]. Therefore, it is of importance to know the effects of ECLE on corneal metabolism and epithelial barrier function.

The green corneal autofluorescence excited by blue light (lez~ = 430-490 nm; tern = 530-600 nm) was found to be an indicator for corneal metabolic activity [3]. This intrinsic fluorescence originates from corneal tissue and can be measured in vivo in a few seconds with fluorophotometry.

The barrier function of the corneal epithelium can be evaluated quantitatively by measurement of the corneal epithelial permeability for fluorescein. This permeability can be calculated from the amount of fluorescein that penetrates the cornea after application of a fluorescein bath to the eye [4].

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A significant difference in corneal swelling response between the cornea of an operated eye and that of the fellow eye has been found after a hypoxic stress on both eyes [5]. The operation was an extracapsular lens extraction (ECLE) or penetrating keratoplasty (PKP) and the stress consisted of keep- ing the corneae hypoxic for two hours. The difference increased with the proportion of the incision [5]. No difference between operated and fellow eye could be found after an osmotic stress test indicating that the swelling properties of the operated corneae were unchanged by surgery [5]. These results give evidence of a difference in oxygen metabolism between both corneae after the operation.

In another study a significantly increased corneal metabolism one year after PKP was found by measuring corneal autofluorescence [3]. Both these studies indicate that a change in corneal autofluorescence after ECLE may be expected.

The corneal epithelial permeability has been found to be increased one week after PKP [6] but was not different from healthy controls 1 year after PKP [7]. These data suggest that an increase in corneal permeability could be expected a few weeks after ECLE.

This study was undertaken to check these sup- positions by measuring corneal autofluorescence and epithelial permeability before and after ECLE with artificial lens implantation.

M a t e r i a l a n d m e t h o d s

Patients

Inclusion criteria: -Planned ECLE with posterior chamber lens

implantation. -Age 35 to 85 years. -Normal aspect of all corneal layers on slit-lamp

examination. Exclusion criteria:

- Ophthalmic medication. - History of eye disease (except cataract). - C o n t a c t lens wear in the 36 hours preceding the

examination. -/3-blocking medication (topical or systemic) [8]. - Diabetes mellitus type I or II [3, 9].

The research followed the tenets of the Declaration of Helsinki and was approved by the Medical Eth- ical Committee of the Leiden University Hospital. Informed consent was obtained from each patient after a verbal and a written explanation of the procedure of the study.

Medication

Medication started one day before surgery by instil-

lation of one drop of Maxitrol| (dexamethasone 1 mg/ml, neomycin sulphate 3.5 mg/ml, polymyxin B sulphate 6000 E/ml, benzalkonium chloride and hydroxypropylmethyl cellulose 0.5%; Alcon, Cham, Switzerland) five times a day and indomethacin 0.1% (Hospital Pharmacy, Leiden, The Netherlands) two times a day. Eye drops of cyclogyl, mydriaticum and phenylephrine (Hospital Pharmacy, Leiden, The Netherlands) were given to maintain mydriasis and cycloplegia during the operation, starting at one hour before surgery. Balanced salt solution was used as ocular irrigation. At the end of the operation all patients received a parabulbar injection of cele-

stone chronodose | (betamethasone disodium phos- phate 4 rag, 3 mg betamethasone acetate in suspension; Schering corporation USA, Kenilworth, NJ, USA) and

a Maxitrol| ointment bandage (Hos- pital Pharmacy, Leiden, The Netherlands).

Postoperatively, one eye drop of Maxitrol| was administered five times a day, and one indomethacin 0.1% eye drop two times a day beginning the day after

surgery. The Maxitrol| treatment was cut back from 5 times a day one drop to 2 times a day one drop within 2 weeks after ECLE and terminated at about 10 weeks. The indomethacin treatment was continued for about 6 weeks postoperatively.

The fellow eye received no medication.

Instrumentation

Fluorophotometric measurements along the optical axis of the eye were carried out with a scanning fluorophotometer (Fluorotron Master, Coherent Radiation Inc., Palo Alto, CA, USA) fitted with a special lens (anterior segment adapter) for detailed scanning of the anterior segment (Figure 1). The scan duration was decreased to 10 seconds in order to reduce the probability of blinking during the scanning.

227

I IOO

0

10 U

i " 5 I 0

Distance alon9 the op t i ca l ax i s ( ~ )

Figure 1. Fluorophotometry of the anterior segment of the eye. Upper part: Schematic representation of the scanning of lenticular and corneal autofluorescence. Fluorophotometric measurements are done step by step by moving the intersection diamond of the exci- tation and fluorescence detection beams along the optical axis of the eye (horizontal dotted line). Lowerpart: Lenticular and corneal autofluorescence scan profile of a patient with a cataractous lens. Note the logarithmic fluorescence axis.

Corneal epithelial permeability

The values of the corneal epithelial permeability of each eye were determined according to a method described previously [4]. Eye baths containing a solution of fluorescein 1% in saline were applied simultaneously to both eyes for 3 minutes. Thereafter the eyes were rinsed several times during 5 minutes with eye baths containing saline only. Then fluorophoto'- metric scans of each eye were performed alternately for one hour (at least 15 scans per eye). The epithelial permeability value of each cornea was calculated from the ratio between the fluorescein concentrations in cornea and eye bath. The fluorescein concentration in the cornea directly after the eye bath was calculated using an exponential regression procedure to the measured peak corneal concentration values as a function of the time after bathing. A correction for fluorescein still present in tears after rinsing was performed if required [4].

Chronological schedule

The corneal thickness was measured with an ultrasonic pachometer (DGH 1000, DGH Technology Inc., San Diego, CA, USA).

Corneal autofluorescence and lenticular tailing

The fluorescence of the cornea can be increased appar- ently by the lenficular autofluorescence as a result of the limited spatial resolution of the fluorophotometer (lenticular tailing; Figure 1). This is especially the case for cataract patients who have lenticular autofluorescence values which are several times higher than those of healthy subjects [10]. Note that the autofluorescence peak value of a healthy lens is about 20 to 100 times that of a healthy cornea [3]. To solve this problem soft- ware was developed to approximate the scan profile of the apparent lenticular autofluorescence under the corneal autofluorescence by an exponential function. The parameters of this function were obtained with the use of a regression procedure to the scan points before and after the corneal signal. The noise in the scan values was reduced with the use of a moving average of 3 consecutive scan points to increase accuracy.

The autofluorescence measurements were calibrat- ed with the use of a reference standard (Zeiss fluorescence reference-F53, Zeiss, Germany).

One week before surgery Slitlamp examination of both eyes was performed to check for a normal aspect of all corneal layers. This was done without fluorescein staining as this would interfere with fluorophotometry. Five fluorophotometric scans of each cornea were performed without using fluorescein, to determine the average corneal autofluorescence. The corneal epithelial permeability values of both eyes were determined by fluorophotometry. After fluorophotometry slitlamp examination was performed using fluorescein in order to detect possible corneal epithelial lesions.

Surgery A standard extracapsular lens extraction with corneal scleral approach was performed with local or general anesthesia. The anterior chamber was opened and cap- sulectomy performed. The lens nucleus was removed and all cortex was evacuated using the pull-push tech- nique. A Pearce Vaulted Tripod lens (Rayner, East Sus- sex, England) was inserted in the capsular bag. After- wards the corneal-scleral wound and the conjunctiva were closed with separate 10-0 nylon and 8-0 virgin silk sutures, respectively [ 11].

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Three to 4 weeks after surgery Corneal autofluorescence and epithelial permeability measurements were performed as described above. Thereafter pachometry of both eyes was performed using a local anesthetic (oxybuprocain 0.4%, Hospi- tal Pharmacy, Leiden, The Netherlands). The corneal thickness was measured five times by touching the centre of the cornea slightly with the transducer of the pachometer. The thickness was measured after the corneal epithelial permeability determination to avoid erroneous fluorophotometric results due to corneal epithelial damage by the pachometry. Pachometry was performed to check whether the corneal thickness had changed more than a few percent since the results of the corneal epithelial permeability measurements depend on corneal thickness [4]. The corneal thickness was determined in the operated eye of the first five patients and in both eyes of the other patients.

One to 4 months after cataract surgery In the period from l to 4 months postoperatively corneal autofluorescence measurements were done in the patients who had given their consent for these extra measurements. The patients were not receiving topical eye medication anymore in this period.

Ten to 12 months after surgery In the period from l0 to 12 months after surgery extra corneal autofluorescence and epithelial permeability measurements were done in patients who had given their consent for these extra measurements to check for a possible long-term effect of the surgery on both corneal parameters.

Effects of topical Maxitrol @

Two healthy volunteers with no history of eye disease

received topical Maxitrol| (3 times a day one eye drop, for a period of 10 days, in one eye only) in

order to check for possible effects of Maxitrol| on the corneal autofluorescence and epithelial permeability. The corneal autofluorescence and permeability of both eyes were measured one day before and on the last day of this treatment.

Effects of topical indomethacin O. 1%

Both eyes of 3 healthy volunteers were measured as well before as 3 hours after one drop of indomethacin 0.1% in one eye only to check for possible short

e

2o

I :)

0

0 0

lens

c o r n e a

c o r r N ~ a

I I I I I ~ 1 I I i 0 3 6 0

D i s t a n c e alon9 the ol~tieal ax is (~ "0

c o r n e a

L 3

Figure 2. Examples of autofluorescence scans of the cornea. Left panel: Eye with a cataractous lens. Middle panel: Same eye as in left panel, after surgery and artificial lens implantation. Rightpanel: Healthy eye without cataract for comparison. The solid vertical line represents the magnitude of the corneal peak autofluorescence and the dotted vertical line the amount of lens tailing.

term effects on both corneal parameters. The three- hour interval was chosen to mimic the situation of the patients.

Two additional healthy volunteers were measured after a prolonged indomethacin 0.1% treatment (twice a day one eye drop in one eye only, for 7 days). This was done in order to check for possible effects due to long term topical indomethacin treatment.

Statistics

The Wilcoxon paired non-parametric signed-rank test was used for the evaluation of differences in both corneal autofluorescence and corneal epithelial permeability values because of the small number of patients, a possible non-normal distribution of the sampled pop- ulation and the large interindividual variability [4]. All P-values are two tailed values unless otherwise specified.

Results

Patients

Eighty percent of 140 consecutive patients attending for cataract surgery were left out of considera- tion because they did not meet the selection criteria. Fourteen patients refused cooperation or were not able to cooperate. Four patients dropped out of the study

229

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0^ :o~ 1,

i I .m 12

n=].O n=4 n=4

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

TiMe a f t e r ECLE su rge r *4 (~ ths )

Figure 3. Mean corneal autofluorescence as a function of time after surgery. LeflpaneI: ECLE eye. Rightpanel: fellow eye. Vertical bars indicate standard error of the mean; n = number of eyes. B = before operation. Note the logarithmic time scale. The solid horizontal line represents the mean corneal autofluorescence value of healthy controls and the broken horizontal lines correspond with the 95% probability intervals [2].

because of: psychological problems, facial dermatitis, complications after surgery requiring additional ocular laser therapy and loss of data due to computer breakdown.

Retrobulbar anesthesia was used in one patient; all other patients received general anesthetics during the cataract surgery. Two patients received additional timo-

lol drops (Merck, Sharp & Dohme, Timoptol| Paris,

France; or Timoptic| Rahway, NJ, USA) to decrease the ocular pressure. No unusual signs of inflammation were found in the eyes of these two patients.

One patient received instead of Maxitrol| topi-

cal Predmycin-P-Liquifilm| (prednisolone acetate 5 mg/ml, neomycin sulphate 5 mg/ml, polymyxin B sulphate 5000 IE/ml, polyvinyl alcohol 1.4%/ml and thiomersal 0.01%/ml; Allergan, Nieuwegein, The Netherlands) because of secondary glaucoma. No surgical complications nor excessive inflammatory reactions were found in the patients.

Corneal autofluorescence

Examples of corneal autofluorescence scans along the optical axis are presented in Figure 2. The corneal autofluorescence of an eye with a cataractous lens is lifted by the tail of the lenticular autofluorescence (left panel). In the same eye after ECLE surgery, fluorescence originating from the implant lens was below the detection limit of the fluorophotometer (1 ng eq. fluorescein/ml) resulting in the absence of lens tailing (Figure 2, middle panel). The lens tailing in a healthy volunteer

'~ 0 , 1

io.C .... o:io I n = t O n : 4

. - ~ g = 4

~o.o . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . = . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . ~..e.., . .~. ~ ~.1_. . . . : . . . . .~ . . . . . . . , . . . . r . .~ . .~ . . , .~ .4 . . . . . . . : . . . . . . . . . . . . . . . ,~.~. .~. . , . . , . , .~. . , . . . . : . . . . .~. . . . . . , . . . . . , . . .~. . , . . , . . , . , .~... . . . .~ ..... O~ 1 2 5 lO i~ O.5 1 2 S 10

T i~e a f t e r KCLE ~urger9 ( n~ ths )

Figure 4. Mean corneal epithelial permeability as a function of time after surgery. Panels and lines as in Figure 3.

proved to cause a small increase of the corneal peak (Figure 2, right panel).

The mean corneal peak autofiuorescence values of all patients (all Caucasians, 8 male, 2 female; mean age: 72.4 years • 11.5 SD; range: 47-85 years) are presented in Figure 3.

The mean corneal autofluorescence value of the operated eye decreased significantly 3-4 weeks after surgery (mean decrease: 14%, P = 0.038, single sided) but not that of the fellow eye (P > 0.25). The mean corneal autofluorescence values of the patients who gave their consent for further measurements at about 2, 3 and 10 months after surgery are presented in Figure 3. All values of both eyes were within the normal range.

The average error in the values of corneal autofluorescence if the correction for lens tailing was omitted amounted to 25% for the ECLE eye and 16% for the fellow eye.


The mean corneal epithelial permeability values of each eye before and after surgery (at 3-4 weeks and one year) are presented in Figure 4. The mean corneal epithelial permeability of the operated eye was significantly increased 3-4 weeks after surgery (average increase: 34%; P = 0.015). The permeability of the fellow eye was also increased (average increase: 32%; P = 0.15). Both values were outside the 95% probability interval for healthy volunteers [4].

The corneal epithelial permeability values of the 4 patients who had given their consent for extra measurements were within normal range nine to twelve months after surgery (both eyes; Figure 4).

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Table 1. Healthy volunteers treated with Maxitrol|

Volunteer Eye # (~L)

Corneal autofluorescence Corneal epithelial permeability Before* After* Before* After* (ngEqml- 1) (ngEqml-l) (nms- 1) (nms-l)

1 R** 12.7 12.7 0.046 0.049 L 13.3 13.1 0.042 0.038

2 R** 9.3 10.1 0.047 0.035 L 10.6 10.3 0.051 0.032

* Before or after receiving topical Maxitrol| treatment in one eye. ** Eye receiving Maxitrol| treatment.

Effects of topical Maxitrol~

The corneal autofluorescence values of both eyes

before and during the Maxitrol | treatment of one eye for 10 days did not differ more than 8% in the two healthy volunteers (Table 1). The corneal epithelial permeability values of both eyes of both volunteers

increased at most 6% after the Maxitrol | treatment (Table 1). All corneal autofluorescence and epithelial permeability values before and after treatment were within normal range [3, 4].

Effects of topical indomethacin

The corneal autofluorescence and corneal epithelial permeability values of both eyes before and 3 hours after indomethacin instillation in one eye are shown in Table 2. After treatment the mean corneal autofluorescence values of the instilled eye and the fellow eye changed - 5% and - 2%, respectively. The mean change in corneal autofluorescence in long term indomethacin- test was - 1% for the instilled eye.

The mean corneal epithelial permeability values of the instilled eye and fellow eye changed - 4% and + 2% respectively, 3 hours after indomethacin instillation. After the long term indomethacin-treatment the mean corneal epithelial permeability of the instilled eye increased 24%.

All layers of the corneae of all healthy volunteers were normal on slitlamp examination as well before as after the indomethacin-test.

Pachometry

The difference in corneal thickness between the operated eye and the fellow eye 3-4 weeks after ECLE was not significant (P = 0.35).

Discussion

Corneal autofluorescence

The corneal autofluorescence values of the operated eye were significantly decreased 3-4 weeks after cataract surgery (mean decrease 14%), indicating a decrease in corneal metabolism [3]. These results corroborate those of another study where stress tests (hypoxic and hypotonic) were used for quantification of corneal metabolism [5] but contradict those from a study on PKP patients where the corneal metabolism showed a significant increase of 31% in comparison with healthy volunteers as quantified by fluorophotometry [3]. This contradiction maybe explained in several ways: 1) the corneal autofluorescence was measured at a shorter time after surgery (this study: 3-4 weeks after ECLE; PKP-study: 4.2 q- 3.7 years [3]). 2) The ECLE incision may not be large enough to induce a significant reaction in corneal metabolism in the long term (incision: 120~ for ECLE, 3600 for PKP). 3) The apparent increase of corneal autofluorescence found after PKP as compared to healthy volunteers may also be attributed to a cataractous lens, since the corneal autofluorescence values were not corrected for lens tailing [3]. The PKP patients have received a topical corticosteroid treatment for a long period after the transplantation (at least one year), which could have induced cataract in the lens, resulting in a high value oflenticular autofluorescence [7, 12].

Note that the corneal autofluorescence values of both corneae of the patients returned simultaneously to preoperative values in about one year (Figure 3).

A medication which could be considered to have an effect on corneal metabolism is Maxitrol| since it contains the corticosteroid dexamethasone. Howev- er, about no effect of Maxitrol | treatment on corneal

Table 2. Healthy volunteers treated with indomethacin 0.1%.

Volunteer Eye Corneal autofluorescence Corneal epithelial permeability (R/L) Before* After* Before* After*

(ngEqml- 1) (ngEqml- 1) (nms-1) (nms-1)

1 R** 10.9 11.3 0.026 0.029 L 10.8 10.6 0.031 0.023

2 R** 10.3 9.6 0.072 0.061 L 12.7 12.4 0.066 0.048

3 R 15.1 14.7 0.052 0.083 L** 16.1 14.4 0.057 0.053

4*** R** 10.9 10.6 0.026 0.028 L 10.8 13.6"*** 0.031 0.058****

5*** R** 13.8 14.0 0.044 0.062 L 12.4 14.5 0.065 0.048

* Before or after receiving topical indomethacin 0.1% treatment in one eye. ** Eye receiving indomethacin 0.1% treatment. *** Healthy controls participating in the extended indomethacin-test (twice a day one drop, for 7 days). **** Very large variation in values due to drifting away of the left eye during the measurements.

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autofluorescence could be found in both healthy volunteers as well in the treated as in the fellow eye (Table 1). Indomethacin may also affect corneal metabolism. No effect of indomethacin treatment on the corneal autofiuorescence could be found (Table 2).

The larger error in the value of the corneal autofluorescence of the ECLE-eye (25%) in comparison with the fellow eye (16%) if the correction for lens tailing had been omitted can be attributed to the more opaque lens in the operated eye, resulting in a higher value of lens tailing. When the corneal autofluorescence is measured the possibility of lens tailing should always be accounted for, especially with patients with cataract or at high risk for cataract.


The corneal epithelium needs an intact neural innervation to perform its function properly [5]. This neural innervation is partly damaged after ECLE due to the incision for cataract extraction. Therefore a change in epithelial barrier function may be expected. The results of this study show a significantly increased corneal epithelial permeability (34%) in the ECLE eye 3 to 4 weeks after cataract extraction. Surprisingly the corneal epithelial permeability of the fellow eye was also increased after cataract surgery (32%). Note that the intraindividual variability in permeability values of healthy volunteers is less than 10% [4]. Such consen-

sual reactions as a result of ECLE in one eye have also been found for the blood aqueous barrier [13, 14]. Oth- er kinds of surgery or therapy have also given evidence of a similar consensual effect as well in humans as in animals [15-17]. Topical eye medication can also be responsible for an increase in corneal epithelial permeability, because of the medication itself, the preservatives used or a combination of both [9, 18]. The topical eye medication used after surgery in our study can reach the general circulation through the conjunctiva of the operated eye and the nasal mucosa as is supposed by other investigators who found a contralateral effect after topical treatment of one eye [19, 20]. On the other hand no increase in corneal epithelial permeability in the contralateral eye after instillation of ophthalmologic solutions with several topical anesthetics or preservatives was found in a previous study [18].

No increase of permeability in excess of 6% was

found in the eyes treated with Maxitrol | and in the fellow eyes of the two healthy volunteers, indicating that the increase found after ECLE can probably not

be attributed to the Maxitrol | treatment. Indomethacin gives in general protection against

breakdown of ocular barriers after surgery [21, 22]. No increasing effect on the corneal epithelial permeability could be found in the short term test in healthy volunteers. The long term indomethacin-test showed a mean increase of + 24% in the instilled eye of healthy

232

volunteers compared to + 34% in patients. In the fel-

low eye the mean increase did not reach the border of 10% of the intralndividual variability (increase in

patients: + 32%) [4]. The fiuorophotometric measure-

ments were performed in a manner analogous to those of the patients, that is at least 3 hours after instillation

of topical eye medication. It can not be excluded that

the increase in permeability in the operated eyes can

be attributed for a part to the use of indomethacin. The

increase in the fellow eye can probably not be attributed to the use of indomethacin.

The permeability values of ECLE- as well as contralateral eyes returned to normal one year after ECLE

(Figure 4) which is also the case with permeability values 3.9 years q- 3.5 SD after PKP [7].

Pachometry

No significant difference in the thickness of the cornea

could be detected between the operated and the fellow

eye 3 to 4 weeks postoperatively. This is in accordance with other studies [5, 23]. As a result, no corrections

were required for the corneal thickness in the calcula-

tion of the corneal epithelial permeability values [4].

Conclusions

The increased value of corneal epithelial permeability still present 3 to 4 weeks after surgery should be

accounted for when eye medication is given. Further-

more it seems recommendable to perform any surgery on the fellow eye at a time exceeding 1 month after

the first surgery because consensual reactions of the

corneal epithelial barrier and the blood aqueous barri-

er may cause an increased predisposition to operative injury.

Consensual reactions should be taken into consid- eration when using the fellow eye as a control for the

evaluation of a treatment. A better control is comparing

the same eye before and after treatment.

Acknowledgment

The authors like to thank E.P.M. Boets Ph.D. for per- forming the pachometric measurements.

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Address for correspondence: J.A. van Best, Department of Oph- thalmology, University Hospital Leiden, PO Box 9600, 2300 RC Leiden, The Netherlands

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