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Specular Microscopy of Hard Contact Lens Wearers II
Specular Microscopy of Hard Contact Lens Wearers II KAZUYOSHI YAMAUCHI, MD/ LAWRENCE W. HIRST, MD/ CHERYL ENGER, MS/ JULIE ROSENFELD, BA,3 WILLIAM VOGELPOHL, MS1
Abstract: Specular microscopy was done on 65 long-term hard contact lens (CL) wearers and controls matched for age, sex, race, and refractive error. There was no difference in mean endothelial cell size between the two groups, although median cell area was slightly smaller in the CL group. Standard deviation and coefficient of variation increased as the duration of total wearing time increased and were greater in the CL group, as was skewness. In 15 long-term hard CL wearers who had discontinued their CL wear, there was a trend towards persistence of pleomorphism and polymegathism of cells compared with noncontact lens (NCL) wearers, but there was a suggestion of recovery compared with those continuing to wear Cls matched for duration of wear. Ophthalmology
96:1176-1179, 1989
A number of studies have examined the acute changes in the corneal endothelium after hard contact lens (CL) wear. 1- 3 Limited studies suggest increased pleomorphism and polymegathism of endothelial cells after long-term hard CL wear. 3- 8 Only one study examined patients who discontinued wearing hard CLs, and this suggested persistence of endothelial changes. 8 We describe the continuation of a study of the corneal endothelium by specular microscopy of hard CL wearers7 and a study of a group of hard CL wearers who discontinued CL use.
PATIENTS AND METHODS Continuing or discontinued CL wearers for this study were recruited using signs posted on hospital bulletin boards and also from patients attending the ophthalmology clinic. The noncontact lens (NCL) wearer control population was recruited by placing requests on bulletin boards in hospitals only; no controls were taken from patients attending the ophthalmology clinic. 7 All patients gave informed consent and were examined at the slit lamp for corneal abnormalities. Patients who Originally received: December 1, 1986. Revision accepted: February 24, 1989. 1 2 3
Bethesda Eye Institute, St. Louis University, St. Louis. Biostatistical Center, Wilmer Institute, Johns Hopkins Hospital, Baltimore. Department of Anatomy, Johns Hopkins University, Baltimore.
Supported in part by Research to Prevent Blindness, Inc., New York, New York. Reprint requests to Lawrence W. Hirst, MD, Department of Ophthalmology, University of Queensland, Princess Alexandra Hospital, Ipswich Rd, Woolloongabba, Brisbane, Australia 4102.
1176
had any observable corneal changes, other anterior segment disease by slit-lamp examination, or a history of diabetes mellitus were excluded from the study. A thorough CL history was taken, with special reference to corneal problems and CL wearing time, and patients who had discontinued CL wear were specifically questioned and medical records examined to elicit the cause for discontinuing CL use. Specular microscopy was done on CL wearers within one-half hour of removal of the lens and immediately after slit-lamp examination in the NCL wearing group. One drop of proparacaine hydrochloride 1% was instilled in each eye and the central (4 to 6 mm) of corneal endothelium was scanned using the Keeler-Konan wide-field specular microscope (X30 cone). Thirty-six frames of Plus X film were taken of each cornea during the scanning process. Two photographs from each cornea of the hard CL wearers and those who had discontinued hard CL wear, and one photograph from each cornea of the NCLwearing control group were printed to a standardized magnification and digitized manually by tracing the outlines on a Hewlett Packard Digitizing Tablet,? Approximately 1200 cells were digitized per CL wearer and 600 cells per control patient. The digitized information was pooled from both eyes of each study patient and from each control. The controls were matched to the continuing and discontinued CL wearing group with respect to age, sex, race, and refractive error. An attempt was made to keep the control within ±4 years of the age of the paired patient. The CL wearers were stratified into three groups based on total hours of wearing time. Descriptive statistics including mean cell area, median, standard deviation (SD), coefficient of variation (CV), and coefficient of skewness
YAMAUCHI et al
•
Table 1. Matching* for Contact Lens Study (n
SPECULAR MICROSCOPY ON HARD CL WEARERS II
=
65)
No. of Matched Pairs
Difference Age (yrs) ±0 ±1
14
23 22
±2 ±3
2
3 1
±4 ±9
Refractive error (diopters) ±1
17 14 9
±2 ±3
11
±4 ±5 ±6 ±7
5 3
6
* Two pairs not matched for sex; racial matching perfect.
were calculated for each subject. Paired t tests were used to compare the CL wearers and controls with respect to mean cell area, median, SO, and CV. The Wilcoxon matched-pairs signed-rank test was used to compare the coefficient of skewness. Linear regression was used to examine correlations between variables. The frequency of outliers (cells larger than 600 Jtm 2 ) was compared between the CL wearers and controls using the chi-square test. An outlier was defined as an observation more than 3 SO away from the mean, assuming the mean cell area to be 300 Jtm 2 with a SO of 100. The NCL wearers, discontinued CL wearers, and continuing CL wearers were compared using the Friedman two-way analysis of variance. 9
RESULTS CONTINUING CONTACT LENS WEARERS
Sixty-five patients continuing to wear hard CLs were matched with 65 controls. The success of matching age, sex, race, and refractive error can be seen in Table 1. Age was matched within ±4 years in all but one of the pairs.
There was no difference in mean cell area between CL wearers and their matched controls in any of the three groups of total wearing time (Table 2), and the median cell area showed only a marginal difference in the intermediate wearing time group, with the CL wearers having a smaller cell size. The most marked changes were noted in the SO and CV of cell size, both between the CL wearers and their matched controls and with increasing total wearing time of the CL wearers. The group with shorter wearing time showed no difference in SO and a marginal difference in CV. The two groups of longer wearing time showed increased variability (SO= 163 Jtm 2 in CL wearers and SO = 98 Jtm 2 in matched controls; P < 0.01) for the group with the longest wearing time, and similarly CV = 0.50 in the CL wearers while CV = 0.30 in the matched controls (P < 0.001) for the same group of subjects. Linear regression results showed that the difference in SO between the CL wearers and matched controls was significantly related to the total length of wearing time (slope = 4.1 X 1o- 4 Jtm 2 per hour wearing time, P = 0.02) indicating the longer the subjects had worn CLs, the more likely they were to have a larger SO of cell areas. A similar relationship was found with CV (slope = 1.2 X 10-6 per hour wearing time, P = 0.003). The distribution of endothelial cells in CL wearers showed an increased skewness over that of matched controls in 52 of 65 pairs (P < 0.001, Wilcoxon matchedpairs signed-rank test). The CL group had a significantly higher frequency of outliers (cells larger than 600 Jtm 2 ) than the controls (P < 0.0001, chi-square test for trend; Table 3). Regression analysis showed that longer wearing time tended to increase the frequency of outliers (slope = 3.6 X w-s, P = 0.04). DISCONTINUED CONTACT LENS WEARERS
Fifteen previous hard CL wearers were examined and compared with: ( 1) matched controls who had never worn CLs and (2) a group of controls who were continuing CL wearers with a similar length of total CL wear. The CL wear had been discontinued 2 to 14 years previously because of lack of motivation and not because of particular corneal problems, according to the patients' histories. The
Table 2. Endothelial Parameters in Contact Lens Wearers and Matched Controls Stratified by Duration of Lifetime Contact Lens Wear Controls
Contact Lens Wearers Lifetime Contact Lens Wear (1 ODDs of hrs)
No.
Mean (!Lm2)
Median (!Lm2)
(!Lm2)
cv
Mean (!Lm2)
Median (!Lm2)
SO (!Lm2)
cv
<50 50-100 >100
19 34 12
309 307 319
290 283* 280
119 132t 163t
0.39* 0.42t 0.5Dt
299 315 325
284 303 313
101 102 98
0.33 0.32 0.30
Total
65
310
285
134
0.43
312
299
101
0.32
so
SO = standard deviation; CV = coefficient of variation = SO/mean. Significance levels based on paired ttests comparing CL patients with matched controls. * P< 0.05. t P< 0.01. t p < 0.00001.
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OPHTHALMOLOGY
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success in matching for the second group is shown in Table 4. There were no differences in the mean or median cell areas between the three groups (Table 5). There was a clear but nonsignificant trend of increasing SD and skewness over the three groups (from no CL wear, to discontinued use, to continuing CL wear) and a significant trend of increasing CV (P = 0.01 ). While some of these differences were not statistically significant, the fact that the discontinued group lies between the two comparison groups indicates the possibility of a recovery process after discontinuing CL wear. These numbers do not reflect the length of time since the subjects discontinued wearing lenses. A multiple regression model of the difference between CL and NCL wearers on total wearing time and years discontinued showed that years discontinued did not have a significant effect on the difference between groups in endothelial cell parameters with the exception of the skewness which decreased as the years discontinued, increased (P = 0.05). Also, a multiple regression model of the difference between discontinued CL wearers and their continuing CL wear controls found no effect of either total wearing time or years since CLs were discontinued in these differences in endothelial cell parameters.
DISCUSSION There appears to be little doubt in the scientific literature that the use of hard CLs induces acute changes in the corneal endothelial layer. 1- 3 With adaption to CLs these changes resolve entirely, as they also do after the CL is removed from the eye. The etiology for these changes remains uncertain and may be related to lactate build up, increased partial pressure of carbon dioxide, or decreased partial pressure of oxygen at the endothelial level.
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•
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Table 3. Frequency of Outliers in Contact Lens Wearers and Controls Percentage of Cells > 600 ~-tm 2
Contact Lens Wearers (n = 65)
Controls (n = 65)
0-1 1-2 2-3 3-4 4-5 . 5-10 10-20 >20
19 12
40 8
3
4
9
10
6 2
6 4 2 3 1 1
Chi-square 7 = 21.4, P = 0.003. Chi-square 1 (trend) = 15.8, P < 0.0001.
Some studies investigated the effects oflong-term hard CL wear on the corneal endothelium. 3- 8 They revealed an apparent increase in pleomorphism of the endothelial layer although the mean endothelial cell area remained comparable to that of age-matched NCL wearers. Only one study examined the effect of discontinuing long-term hard CL wear. This study suggested a possible persistence of endothelial changes. 8 Our study is the largest undertaken, the only one in which matching was done for refractive error and for age, and the only one where larger samples of endothelial cells were studied. Refractive error as a confounding variable was excluded since most CL wearers have considerable myopia. As many studies have suggested an increase in endothelial polymegathism and pleomorphism with increasing age, to-!2 close age matching tends to reduce the effect of this confounding variable. Our study confirms the irregularity in cell size and shape after long-term hard CL wear despite what might appear to be a normal endothelial density. The cellular changes in the CL group became more apparent with increasing wearing time, sug-
Table 4. Matching for Discontinued and Continuing Contact Lens Wearers Discontinued
Continuing
Age (yrs)/ Race/Sex
Duration of Wear (hrs per day jyrs)
Lifetime Wear (hrs)
Age (yrs)/ RacejSex
Duration of Wear (hrs per day jyrs)
Lifetime Wear (hrs)
37/W/M 30/W/F 26/W/F 29/W/F 38/W/F 28/W/F 50/W/F 30/W/F 43/W/M 34/W/F 25/W/F 34/W/F 38/W/F 45/W/F 52/W/F
10/3 15/3 18/3 14/4 12/7 12/8 14/7 12/10 12/10 12/12 18/9 18/10 10/18 16/16 18/18
10,950 16,425 19,710 20,440 30,660 35,040 35,770 43,800 43,800 52,560 59,130 65,700 65,700 93,440 118,260
31/W/F 33/W/F 23/W/F 33/W/F 32/W/F 24/W/F 55/W/F 30/W/F 41/W/M 27/W/M 24/W/F 27/W/F 34/W /F 40/W/F 51/W/F
16/2 12/5 16/4 14/4 15/6 12/8 10/7 10/12 8/15 14/10 16/10 15/11 10/19 16/15 16/25
11,680 21,900 23,360 20,440 32,850 35,040 25,550 43,800 43,800 51' 100 58,400 60,225 69,350 87,600 146,000
W =white.
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YAMAUCHI et al
SPECULAR MICROSCOPY ON HARD CL WEARERS II
•
Table 5. Endothelial Parameters of Discontinued Contact Lens Wearers Compared with Noncontact Lens Wearers and Continuing Contact Lens Wearers
Mean (~m 2) Median (~m 2) SO (~m 2) Coefficient of variation Test statistic for skewness Outliers(%)
No Contact Lens Controls
Discontinued Contact Lens Wearers
Continued Contact Lens Wearers
P*
329 302 98 0.29
299 274 108 0.32
313 286 112 0.38
0.25 0.15 0.42 0.01
7.0 0.67
9.6 1.38
10.6 1.56
0.09 0.35
SO = standard deviation. No. in table represents median value of the 15 subjects. * Based on Friedman two-way analysis of variance.
gesting that there was an ongoing effect of the CL although ultimate corneal endothelial failure was not commonly observed. Small and large cells appeared to dominate the endothelial layer in the hard CL wearers. The small cells appeared to be grouped together in clusters, as were the large cells. Although this form of pleomorphism has been described previously, 7•8 its clinical significance is unclear. It does not appear similar to reformation "figures." Comparison of patients who have discontinued their hard CL wear with controls who have never worn CLs did not produce a statistically significant difference, although there appeared to be a trend toward increasing variation in cell size and shape in the discontinued hard CL wearing group. Similarly, comparing the discontinued hard CL wearers against those matched controls continuing to wear hard CLs did not show a difference between the two groups. This could be explained by insufficient sample size or by some resolution of variation in cell size and shape in those patients discontinuing CL wear, which would place the pleomorphism of their endothelial layer between those patients continuing to wear CLs and those who have never worn them. Only examination of a larger patient group will be able to confirm one of these hypotheses. All studies of hard CL wearers, including ours, suffer from the potential sampling errors and observer biases of specular microscopy. 13 These sampling problems may be less of a problem in our study because of the widespread nature of the endothelial changes that equilibrated over the endothelial layer for a long period of time. However, the clustering of cells as observed in these CL wearers makes all studies purporting to show a statistically significant difference and the quantity of this difference suspect. Too much reliance, therefore, should not be placed
upon the actual quantitative results of the sampling of wide-field specular microscopy. The etiology of the changes in the endothelial layer of hard CL wearers is obscure but probably reflects a function of long-term relative anoxia of the endothelial layer. Whether it is a change in pH, a change in the partial pressure of oxygen or carbon dioxide, or lactate accumulation has not been eludicated. The clinical significance of our findings remains unclear because none of these patients have obvious signs of endothelial dysfunction. However, other studies have suggested a correlation between endothelial pleomorphism and polymegathism and a decreased reserve and resistence to further endothelial trauma. 14 The effect of this upon the continuing CL wearing group when undergoing future surgery cannot be estimated. None of the studies are conclusive enough in either their results or in the significance of the results so that hard contact lens wearers should be actively persuaded to discontinue wearing their lenses.
REFERENCES 1. Zantos SG, Holden BA. Transient endothelial changes soon after wearing soft contact lenses. Am J Optom Physiol Opt 1977; 54:856-8. 2. Holden BA, Williams L, Zantos SG. The etiology of transient endothelial changes in the human cornea. Invest Ophthalmol Vis Sci 1985; 26: 1354-9. 3. Bergmanson JPG, Chu LW·F. Corneal response to rigid contact lens wear. Br J Ophthalrnol1982; 66:667-75. 4. Barr JT, Schoessler JP. Corneal endothelial response to rigid contact lenses. Am J Optom Physiol Opt 1980; 57:267-74. 5. Schoessler JP, Woloschak MJ. Corneal endothelium in veteran PMMA contact lens wearers. lnt Contact Lens Clin 1981; 8:19-25. 6. Caldwell DR, Kastl PR, Dabezies OH, et al. The effect of long-term hard contact lens wear on corneal endothelium. Contact lntraocul Lens Med J 1982; 8:87-91. 7. Hirst LW, Auer C, Cohn J, et al. Specular microscopy of hard contact lens wearers. Ophthalmology 1984; 91:1147-53. 8. MacRae SM, Matsuda M, Shellans S, Rich LF. The effects of hard and soft contact lenses on the corneal endothelium. Am J Ophthal· mology 1986; 102:50-7. 9. Siegel S. Nonpararnetric Statistics for the Behavioral Sciences. New York: McGraw-Hill, 1956; 75-83. 10. Laing RA, Sandstrom MM, Berrospi AR, Leibowitz HM. Changes in the corneal endothelium as a function of age. Exp Eye Res 1976; 22: 587-94. 11. Suda T. Mosaic pattern changes in human corneal endothelium with age. Jpn J Ophthalrnol1984; 28:331-8. 12. Yee RW, Matsuda M, Schultz RO, Edelhauser HF. Changes in the normal corneal endothelial cellular pattern as a function of age. Curr Eye Res 1985; 4:671-8. 13. Hirst LW, Auer C, Abbey H, et al. Quantitative analysis of wide-field endothelial specular photomicrographs. Am J Ophthalmol1984; 97: 488-95. 14. Shaw EL, Rao GN, Arthur EJ, Aquavella JV. The functional reserve of corneal endothelium. Ophthalmology 1978; 85:640-9.
1179
Abstract: Specular microscopy was done on 65 long-term hard contact lens (CL) wearers and controls matched for age, sex, race, and refractive error. There was no difference in mean endothelial cell size between the two groups, although median cell area was slightly smaller in the CL group. Standard deviation and coefficient of variation increased as the duration of total wearing time increased and were greater in the CL group, as was skewness. In 15 long-term hard CL wearers who had discontinued their CL wear, there was a trend towards persistence of pleomorphism and polymegathism of cells compared with noncontact lens (NCL) wearers, but there was a suggestion of recovery compared with those continuing to wear Cls matched for duration of wear. Ophthalmology
96:1176-1179, 1989
A number of studies have examined the acute changes in the corneal endothelium after hard contact lens (CL) wear. 1- 3 Limited studies suggest increased pleomorphism and polymegathism of endothelial cells after long-term hard CL wear. 3- 8 Only one study examined patients who discontinued wearing hard CLs, and this suggested persistence of endothelial changes. 8 We describe the continuation of a study of the corneal endothelium by specular microscopy of hard CL wearers7 and a study of a group of hard CL wearers who discontinued CL use.
PATIENTS AND METHODS Continuing or discontinued CL wearers for this study were recruited using signs posted on hospital bulletin boards and also from patients attending the ophthalmology clinic. The noncontact lens (NCL) wearer control population was recruited by placing requests on bulletin boards in hospitals only; no controls were taken from patients attending the ophthalmology clinic. 7 All patients gave informed consent and were examined at the slit lamp for corneal abnormalities. Patients who Originally received: December 1, 1986. Revision accepted: February 24, 1989. 1 2 3
Bethesda Eye Institute, St. Louis University, St. Louis. Biostatistical Center, Wilmer Institute, Johns Hopkins Hospital, Baltimore. Department of Anatomy, Johns Hopkins University, Baltimore.
Supported in part by Research to Prevent Blindness, Inc., New York, New York. Reprint requests to Lawrence W. Hirst, MD, Department of Ophthalmology, University of Queensland, Princess Alexandra Hospital, Ipswich Rd, Woolloongabba, Brisbane, Australia 4102.
1176
had any observable corneal changes, other anterior segment disease by slit-lamp examination, or a history of diabetes mellitus were excluded from the study. A thorough CL history was taken, with special reference to corneal problems and CL wearing time, and patients who had discontinued CL wear were specifically questioned and medical records examined to elicit the cause for discontinuing CL use. Specular microscopy was done on CL wearers within one-half hour of removal of the lens and immediately after slit-lamp examination in the NCL wearing group. One drop of proparacaine hydrochloride 1% was instilled in each eye and the central (4 to 6 mm) of corneal endothelium was scanned using the Keeler-Konan wide-field specular microscope (X30 cone). Thirty-six frames of Plus X film were taken of each cornea during the scanning process. Two photographs from each cornea of the hard CL wearers and those who had discontinued hard CL wear, and one photograph from each cornea of the NCLwearing control group were printed to a standardized magnification and digitized manually by tracing the outlines on a Hewlett Packard Digitizing Tablet,? Approximately 1200 cells were digitized per CL wearer and 600 cells per control patient. The digitized information was pooled from both eyes of each study patient and from each control. The controls were matched to the continuing and discontinued CL wearing group with respect to age, sex, race, and refractive error. An attempt was made to keep the control within ±4 years of the age of the paired patient. The CL wearers were stratified into three groups based on total hours of wearing time. Descriptive statistics including mean cell area, median, standard deviation (SD), coefficient of variation (CV), and coefficient of skewness
YAMAUCHI et al
•
Table 1. Matching* for Contact Lens Study (n
SPECULAR MICROSCOPY ON HARD CL WEARERS II
=
65)
No. of Matched Pairs
Difference Age (yrs) ±0 ±1
14
23 22
±2 ±3
2
3 1
±4 ±9
Refractive error (diopters) ±1
17 14 9
±2 ±3
11
±4 ±5 ±6 ±7
5 3
6
* Two pairs not matched for sex; racial matching perfect.
were calculated for each subject. Paired t tests were used to compare the CL wearers and controls with respect to mean cell area, median, SO, and CV. The Wilcoxon matched-pairs signed-rank test was used to compare the coefficient of skewness. Linear regression was used to examine correlations between variables. The frequency of outliers (cells larger than 600 Jtm 2 ) was compared between the CL wearers and controls using the chi-square test. An outlier was defined as an observation more than 3 SO away from the mean, assuming the mean cell area to be 300 Jtm 2 with a SO of 100. The NCL wearers, discontinued CL wearers, and continuing CL wearers were compared using the Friedman two-way analysis of variance. 9
RESULTS CONTINUING CONTACT LENS WEARERS
Sixty-five patients continuing to wear hard CLs were matched with 65 controls. The success of matching age, sex, race, and refractive error can be seen in Table 1. Age was matched within ±4 years in all but one of the pairs.
There was no difference in mean cell area between CL wearers and their matched controls in any of the three groups of total wearing time (Table 2), and the median cell area showed only a marginal difference in the intermediate wearing time group, with the CL wearers having a smaller cell size. The most marked changes were noted in the SO and CV of cell size, both between the CL wearers and their matched controls and with increasing total wearing time of the CL wearers. The group with shorter wearing time showed no difference in SO and a marginal difference in CV. The two groups of longer wearing time showed increased variability (SO= 163 Jtm 2 in CL wearers and SO = 98 Jtm 2 in matched controls; P < 0.01) for the group with the longest wearing time, and similarly CV = 0.50 in the CL wearers while CV = 0.30 in the matched controls (P < 0.001) for the same group of subjects. Linear regression results showed that the difference in SO between the CL wearers and matched controls was significantly related to the total length of wearing time (slope = 4.1 X 1o- 4 Jtm 2 per hour wearing time, P = 0.02) indicating the longer the subjects had worn CLs, the more likely they were to have a larger SO of cell areas. A similar relationship was found with CV (slope = 1.2 X 10-6 per hour wearing time, P = 0.003). The distribution of endothelial cells in CL wearers showed an increased skewness over that of matched controls in 52 of 65 pairs (P < 0.001, Wilcoxon matchedpairs signed-rank test). The CL group had a significantly higher frequency of outliers (cells larger than 600 Jtm 2 ) than the controls (P < 0.0001, chi-square test for trend; Table 3). Regression analysis showed that longer wearing time tended to increase the frequency of outliers (slope = 3.6 X w-s, P = 0.04). DISCONTINUED CONTACT LENS WEARERS
Fifteen previous hard CL wearers were examined and compared with: ( 1) matched controls who had never worn CLs and (2) a group of controls who were continuing CL wearers with a similar length of total CL wear. The CL wear had been discontinued 2 to 14 years previously because of lack of motivation and not because of particular corneal problems, according to the patients' histories. The
Table 2. Endothelial Parameters in Contact Lens Wearers and Matched Controls Stratified by Duration of Lifetime Contact Lens Wear Controls
Contact Lens Wearers Lifetime Contact Lens Wear (1 ODDs of hrs)
No.
Mean (!Lm2)
Median (!Lm2)
(!Lm2)
cv
Mean (!Lm2)
Median (!Lm2)
SO (!Lm2)
cv
<50 50-100 >100
19 34 12
309 307 319
290 283* 280
119 132t 163t
0.39* 0.42t 0.5Dt
299 315 325
284 303 313
101 102 98
0.33 0.32 0.30
Total
65
310
285
134
0.43
312
299
101
0.32
so
SO = standard deviation; CV = coefficient of variation = SO/mean. Significance levels based on paired ttests comparing CL patients with matched controls. * P< 0.05. t P< 0.01. t p < 0.00001.
1177
OPHTHALMOLOGY
•
AUGUST 1989
success in matching for the second group is shown in Table 4. There were no differences in the mean or median cell areas between the three groups (Table 5). There was a clear but nonsignificant trend of increasing SD and skewness over the three groups (from no CL wear, to discontinued use, to continuing CL wear) and a significant trend of increasing CV (P = 0.01 ). While some of these differences were not statistically significant, the fact that the discontinued group lies between the two comparison groups indicates the possibility of a recovery process after discontinuing CL wear. These numbers do not reflect the length of time since the subjects discontinued wearing lenses. A multiple regression model of the difference between CL and NCL wearers on total wearing time and years discontinued showed that years discontinued did not have a significant effect on the difference between groups in endothelial cell parameters with the exception of the skewness which decreased as the years discontinued, increased (P = 0.05). Also, a multiple regression model of the difference between discontinued CL wearers and their continuing CL wear controls found no effect of either total wearing time or years since CLs were discontinued in these differences in endothelial cell parameters.
DISCUSSION There appears to be little doubt in the scientific literature that the use of hard CLs induces acute changes in the corneal endothelial layer. 1- 3 With adaption to CLs these changes resolve entirely, as they also do after the CL is removed from the eye. The etiology for these changes remains uncertain and may be related to lactate build up, increased partial pressure of carbon dioxide, or decreased partial pressure of oxygen at the endothelial level.
•
VOLUME 96
•
NUMBER 8
Table 3. Frequency of Outliers in Contact Lens Wearers and Controls Percentage of Cells > 600 ~-tm 2
Contact Lens Wearers (n = 65)
Controls (n = 65)
0-1 1-2 2-3 3-4 4-5 . 5-10 10-20 >20
19 12
40 8
3
4
9
10
6 2
6 4 2 3 1 1
Chi-square 7 = 21.4, P = 0.003. Chi-square 1 (trend) = 15.8, P < 0.0001.
Some studies investigated the effects oflong-term hard CL wear on the corneal endothelium. 3- 8 They revealed an apparent increase in pleomorphism of the endothelial layer although the mean endothelial cell area remained comparable to that of age-matched NCL wearers. Only one study examined the effect of discontinuing long-term hard CL wear. This study suggested a possible persistence of endothelial changes. 8 Our study is the largest undertaken, the only one in which matching was done for refractive error and for age, and the only one where larger samples of endothelial cells were studied. Refractive error as a confounding variable was excluded since most CL wearers have considerable myopia. As many studies have suggested an increase in endothelial polymegathism and pleomorphism with increasing age, to-!2 close age matching tends to reduce the effect of this confounding variable. Our study confirms the irregularity in cell size and shape after long-term hard CL wear despite what might appear to be a normal endothelial density. The cellular changes in the CL group became more apparent with increasing wearing time, sug-
Table 4. Matching for Discontinued and Continuing Contact Lens Wearers Discontinued
Continuing
Age (yrs)/ Race/Sex
Duration of Wear (hrs per day jyrs)
Lifetime Wear (hrs)
Age (yrs)/ RacejSex
Duration of Wear (hrs per day jyrs)
Lifetime Wear (hrs)
37/W/M 30/W/F 26/W/F 29/W/F 38/W/F 28/W/F 50/W/F 30/W/F 43/W/M 34/W/F 25/W/F 34/W/F 38/W/F 45/W/F 52/W/F
10/3 15/3 18/3 14/4 12/7 12/8 14/7 12/10 12/10 12/12 18/9 18/10 10/18 16/16 18/18
10,950 16,425 19,710 20,440 30,660 35,040 35,770 43,800 43,800 52,560 59,130 65,700 65,700 93,440 118,260
31/W/F 33/W/F 23/W/F 33/W/F 32/W/F 24/W/F 55/W/F 30/W/F 41/W/M 27/W/M 24/W/F 27/W/F 34/W /F 40/W/F 51/W/F
16/2 12/5 16/4 14/4 15/6 12/8 10/7 10/12 8/15 14/10 16/10 15/11 10/19 16/15 16/25
11,680 21,900 23,360 20,440 32,850 35,040 25,550 43,800 43,800 51' 100 58,400 60,225 69,350 87,600 146,000
W =white.
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•
Table 5. Endothelial Parameters of Discontinued Contact Lens Wearers Compared with Noncontact Lens Wearers and Continuing Contact Lens Wearers
Mean (~m 2) Median (~m 2) SO (~m 2) Coefficient of variation Test statistic for skewness Outliers(%)
No Contact Lens Controls
Discontinued Contact Lens Wearers
Continued Contact Lens Wearers
P*
329 302 98 0.29
299 274 108 0.32
313 286 112 0.38
0.25 0.15 0.42 0.01
7.0 0.67
9.6 1.38
10.6 1.56
0.09 0.35
SO = standard deviation. No. in table represents median value of the 15 subjects. * Based on Friedman two-way analysis of variance.
gesting that there was an ongoing effect of the CL although ultimate corneal endothelial failure was not commonly observed. Small and large cells appeared to dominate the endothelial layer in the hard CL wearers. The small cells appeared to be grouped together in clusters, as were the large cells. Although this form of pleomorphism has been described previously, 7•8 its clinical significance is unclear. It does not appear similar to reformation "figures." Comparison of patients who have discontinued their hard CL wear with controls who have never worn CLs did not produce a statistically significant difference, although there appeared to be a trend toward increasing variation in cell size and shape in the discontinued hard CL wearing group. Similarly, comparing the discontinued hard CL wearers against those matched controls continuing to wear hard CLs did not show a difference between the two groups. This could be explained by insufficient sample size or by some resolution of variation in cell size and shape in those patients discontinuing CL wear, which would place the pleomorphism of their endothelial layer between those patients continuing to wear CLs and those who have never worn them. Only examination of a larger patient group will be able to confirm one of these hypotheses. All studies of hard CL wearers, including ours, suffer from the potential sampling errors and observer biases of specular microscopy. 13 These sampling problems may be less of a problem in our study because of the widespread nature of the endothelial changes that equilibrated over the endothelial layer for a long period of time. However, the clustering of cells as observed in these CL wearers makes all studies purporting to show a statistically significant difference and the quantity of this difference suspect. Too much reliance, therefore, should not be placed
upon the actual quantitative results of the sampling of wide-field specular microscopy. The etiology of the changes in the endothelial layer of hard CL wearers is obscure but probably reflects a function of long-term relative anoxia of the endothelial layer. Whether it is a change in pH, a change in the partial pressure of oxygen or carbon dioxide, or lactate accumulation has not been eludicated. The clinical significance of our findings remains unclear because none of these patients have obvious signs of endothelial dysfunction. However, other studies have suggested a correlation between endothelial pleomorphism and polymegathism and a decreased reserve and resistence to further endothelial trauma. 14 The effect of this upon the continuing CL wearing group when undergoing future surgery cannot be estimated. None of the studies are conclusive enough in either their results or in the significance of the results so that hard contact lens wearers should be actively persuaded to discontinue wearing their lenses.
REFERENCES 1. Zantos SG, Holden BA. Transient endothelial changes soon after wearing soft contact lenses. Am J Optom Physiol Opt 1977; 54:856-8. 2. Holden BA, Williams L, Zantos SG. The etiology of transient endothelial changes in the human cornea. Invest Ophthalmol Vis Sci 1985; 26: 1354-9. 3. Bergmanson JPG, Chu LW·F. Corneal response to rigid contact lens wear. Br J Ophthalrnol1982; 66:667-75. 4. Barr JT, Schoessler JP. Corneal endothelial response to rigid contact lenses. Am J Optom Physiol Opt 1980; 57:267-74. 5. Schoessler JP, Woloschak MJ. Corneal endothelium in veteran PMMA contact lens wearers. lnt Contact Lens Clin 1981; 8:19-25. 6. Caldwell DR, Kastl PR, Dabezies OH, et al. The effect of long-term hard contact lens wear on corneal endothelium. Contact lntraocul Lens Med J 1982; 8:87-91. 7. Hirst LW, Auer C, Cohn J, et al. Specular microscopy of hard contact lens wearers. Ophthalmology 1984; 91:1147-53. 8. MacRae SM, Matsuda M, Shellans S, Rich LF. The effects of hard and soft contact lenses on the corneal endothelium. Am J Ophthal· mology 1986; 102:50-7. 9. Siegel S. Nonpararnetric Statistics for the Behavioral Sciences. New York: McGraw-Hill, 1956; 75-83. 10. Laing RA, Sandstrom MM, Berrospi AR, Leibowitz HM. Changes in the corneal endothelium as a function of age. Exp Eye Res 1976; 22: 587-94. 11. Suda T. Mosaic pattern changes in human corneal endothelium with age. Jpn J Ophthalrnol1984; 28:331-8. 12. Yee RW, Matsuda M, Schultz RO, Edelhauser HF. Changes in the normal corneal endothelial cellular pattern as a function of age. Curr Eye Res 1985; 4:671-8. 13. Hirst LW, Auer C, Abbey H, et al. Quantitative analysis of wide-field endothelial specular photomicrographs. Am J Ophthalmol1984; 97: 488-95. 14. Shaw EL, Rao GN, Arthur EJ, Aquavella JV. The functional reserve of corneal endothelium. Ophthalmology 1978; 85:640-9.
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