Central Corneal Thickness: Congenital Cataracts and Aphakia

Central Corneal Thickness: Congenital Cataracts and Aphakia KELLY W. MUIR, LOIS DUNCAN, LAURA B. ENYEDI, DAVID K. WALLACE, AND SHARON F. FREEDMAN ● PURPOSE:

To evaluate central corneal thickness (CCT) in normal children (controls) and in those with cataracts, pseudophakia, and aphakia. ● DESIGN: Prospective, observational case series. ● METHODS: CCT was measured in 369 eyes of 223 children. Subjects with glaucoma, anterior segment abnormalities, or intraocular pressure of more than 30 mm Hg were excluded. Group means were compared for controls and for eyes with pediatric cataracts, pseudophakia, and aphakia. ● RESULTS: The mean CCT of eyes with cataracts was more than that of controls (574 ⴞ 54 ␮m [n ⴝ 46] and 552 ⴞ 38 ␮m [n ⴝ 230], respectively; P ⴝ .001). After excluding from the cataract group those eyes with aniridia, Down syndrome, Marfan syndrome, or glaucoma surgery, the mean CCT (564 ⴞ 34 ␮m [n ⴝ 36]) was no longer greater than that of controls (P ⴝ .07). The mean CCT of pseudophakic eyes (598 ⴞ 56 ␮m [n ⴝ 29]) was greater than the mean CCT of controls (P < .001) and was similar to the mean CCT of eyes with cataracts (P ⴝ .06). The mean CCT of aphakic eyes (642 ⴞ 88 ␮m [n ⴝ 64]) was greater than the mean CCT of controls (P < .001), eyes with cataracts (P < .001), and eyes with pseudophakia (P ⴝ .003). ● CONCLUSIONS: In the absence of factors known to affect CCT (Down syndrome, Marfan syndrome, and aniridia), CCT is similar in eyes with pediatric cataracts and normal controls and increases after cataract surgery. (Am J Ophthalmol 2007;144:502–506. © 2007 by Elsevier Inc. All rights reserved.)

G

OLDMANN APPLANATION TONOMETRY HAS BEEN

the gold standard for intraocular pressure (IOP) measurement since its introduction in 1956.1 But variability in central corneal thickness (CCT) affects applanation tonometry measurement in both adults2,3 and children.4,5 Children with a history of congenital cataracts who are aphakic or pseudophakic have thicker central corneas than healthy controls,6,7 but it is unknown if the increased CCT predates the surgery or develops after surgery. Glaucoma is a common consequence of surgery for congenital cataracts,8 and recognizing abnormal CCT may be important in the management of pediatric pseudophaAccepted for publication Jun 1, 2007. From the Duke University Eye Center, Durham, North Carolina. Inquiries to Sharon F. Freedman, Duke University Medical Center, Box 3802, Durham, NC 27710; e-mail: [email protected]

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kic and aphakic glaucoma because of the effect of CCT on IOP measurement. We have observed that many eyes with congenital cataracts have normal CCT before surgery and that many aphakic and pseudophakic eyes have increased CCT. We hypothesize that the corneas of most eyes with congenital cataracts are normal and that increased CCT develops after surgery.

METHODS ● SUBJECTS:

Children seeking treatment at the Pediatric Ophthalmology Clinic of Duke University Eye Center from February 2004 through February 2007 were recruited to participate in the study. Subjects were included who had a history of childhood cataracts or who were healthy controls. Healthy controls were excluded if they had glaucoma (either a diagnosis of glaucoma by the treating physician or a history of medical or surgical intervention designed to lower IOP), anterior segment abnormalities, or IOP of more than 30 mm Hg. Subjects identified as glaucoma suspects based on the appearance of optic nerves suspicious for but not diagnostic of glaucoma, but who were not receiving treatment to reduce IOP, were included in the control group. Exclusion criteria included age more than 18 years and inability to cooperate with CCT measurement if an examination under anesthesia was not indicated for other reasons.

● DATA COLLECTION: Data collected from the medical records included age, gender, ocular diagnosis, medical therapy, history of surgery, corneal diameter, and axial length. A corneal diameter of less than 10 mm was considered to be consistent with microcornea, and an axial length of less than 17 mm was considered to be microphthalmos. Standard measurement of CCT was performed as described in a previously reported study.4 Briefly, after topical proparacaine was instilled into the eye for corneal anesthesia, the probe of the ultrasound pachymeter was touched to the center of the cornea and four to six measurements were recorded. The same pachymeter (DGH 500; DGH Technology, Inc, Exton, Pennsylvania, USA) was used for each measurement. ● STATISTICAL METHODS:

Each eye of each subject was treated individually. Values are reported as mean ⫾ stan-

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TABLE 1. Demographic Information by Subject Group (Control, Young Control, Cataract, Pseudophakia, Aphakia)

Gender (%) Male Female Race (%) White Black Hispanic Asian Other Age (yrs)† Mean Median

Control

Young Control*

Cataract

Pseudophakia

Aphakia

60 (51) 58 (49)

16 (64) 9 (36)

18 (60) 12 (40)

13 (57) 10 (43)

26 (63) 15 (37)

58 (49) 47 (40) 2 (2) 8 (7) 3 (3)

10 (40) 11 (44) 0 1 (4) 3 (12)

21 (70) 7 (23) 0 0 2 (7)

17 (74) 5 (22) 1 (4) 0 0

30 (77) 6 (15) 2 (5) 1 (2) 0

10 10

5 6

3 1

7 6

7 6

*The 25 youngest control subjects. † Age of controls was greater than the age of other groups: P ⬍ .001 for control vs each of the other groups.

dard deviation unless otherwise noted. Group means were compared with an unpaired Student t test. P values ⬍ .05 (two sided) were considered significant. Linear regression was used to evaluate the possible relationship of CCT with increasing age. The Fisher exact test was used to compare categorical variables (Graphpad prism software version 2.01, 1996; Graphpad Software, Inc, San Diego, California, USA).

RESULTS THREE HUNDRED SEVENTY EYES OF 223 SUBJECTS WERE

included. There were 117 males and 106 females, and the mean age was eight ⫾ four years (range, 13 days to 17 years). Self-reported race included 135 Whites, 66 Blacks, five Latinos, nine Asians, and eight subjects of other race. Demographic data is presented in Table 1. Of the 230 healthy eyes of 118 controls, CCT data from 178 eyes were reported in a previous study.9 One hundred and thirty-four of the healthy eyes were considered glaucoma suspects based on an increased cup-to-disk ratio but did not receive glaucoma therapy and had an IOP of less than 30 mm Hg. The mean CCT of the control eyes was 552 ⫾ 38 ␮m (n ⫽ 230). The mean CCT of all eyes with cataracts was more than that of control eyes (574 ⫾ 54 ␮m [n ⫽ 46] vs 552 ⫾ 38 ␮m [n ⫽ 230], respectively; P ⫽ .001). The mean CCT of pseudophakic eyes, 598 ⫾ 56 ␮m (n ⫽ 29), was greater than that of control eyes (P ⬍ .001) and was not statistically greater than that of eyes with cataracts (P ⫽ .06). The CCT of aphakic eyes, 642 ⫾ 88 ␮m (n ⫽ 64), was greater than that of control eyes (P ⬍ .001), eyes with cataracts (P ⬍ .001), and pseudophakic eyes (P ⫽ .003). VOL. 144, NO. 4

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FIGURE 1. Graph demonstrating the central corneal thickness (CCT) by diagnostic groups: controls, young controls, cataract, pseudophakia, aphakia, excluding those subjects with conditions known to be associated with abnormal CCT such as Down syndrome, aniridia, and Marfan syndrome: controls (n ⴝ 230), young controls (eyes of 25 youngest subjects in control group, n ⴝ 49), unoperated cataracts (n ⴝ 35), pseudophakia with a history of pediatric cataract (n ⴝ 22), and aphakia with a history of pediatric cataract (n ⴝ 56). Data points represent individual eyes. Bars represent median CCT. The larger control and the smaller young control groups had similar mean CCT (552 ⴞ 38 ␮m vs 557 ⴞ 35 ␮m, respectively; P ⴝ .4). The difference in mean CCT between the eyes with unoperated cataracts (564 ⴞ 34 ␮m) and that of both the control and young control groups was not significant (P ⴝ .07 for both). By contrast, the mean CCT of both the pseudophakic eyes (600 ⴞ 49 ␮m) and the aphakic eyes (633 ⴞ 87 ␮m) was thicker than that of both the control eyes (P < .001) and those with cataracts (P < .001).

Some of the eyes with cataracts, pseudophakia, or aphakia had a history of glaucoma surgery or carried diagnoses known to be associated with abnormal CCT such as Down syndrome,10 aniridia,11 and Marfan syndrome.12 We therefore re-analyzed our data excluding eyes in any of the above categories from the cataract, pseudophakia, and aphakia groups. After excluding these eyes, there was no statistically significant difference in mean CCT of eyes with cataracts compared with control eyes (564 ⫾ 34 ␮m [n ⫽ 35] vs 552 ⫾ 38 ␮m [n ⫽ 230], respectively; P ⫽ .07; Figure 1). Of the nine subjects with unilateral congenital cataracts, the CCT of the cataractous eyes was similar to that of the normal eyes (566 ⫾ 33 ␮m and 563 ⫾ 32 ␮m, respectively; P ⫽ .7; average difference, 2.6 ⫾ 18.6 ␮m). There was a good correlation between the CCT of eyes with unilateral cataract and the fellow eye of the same child (r2 ⫽ 0.70; Figure 2). We did not find a significant difference in the mean CCT depending on the type of cataract present (Table 2). Excluding subjects with Down syndrome, aniridia, Marfan syndrome, or previous glaucoma surgery, the pseudophakic eyes had thicker mean CCT (600 ⫾ 49 ␮m; n ⫽ 22) than control eyes (P ⬍ .001) and eyes with cataracts (P ⫽ .002). With similar exclusions, the aphakic eyes also had thicker mean CCT (633 ⫾ 87 ␮m [n ⫽ 56]) than both the control eyes (P ⬍ .001) and those with cataracts (P ⬍ .001). Within this aphakic

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FIGURE 3. Graph demonstrating the correlation of time after cataract removal and central corneal thickness (CCT) in aphakic eyes without glaucoma. Plotted is the time in years after cataract removal of aphakic eyes without glaucoma vs CCT in micrometers. The slope is nonzero (P < .001), and there is a correlation between the increased time after cataract removal and increased CCT (r2 ⴝ 0.6).

FIGURE 2. Graph demonstrating the correlation of central corneal thickness (CCT) between a cataractous eye and fellow eye in children with unilateral cataracts. Plotted is the CCT of nine pediatric eyes with unilateral cataract (x-axis) vs CCT of normal fellow eye of the same subject (y-axis). The slope is nonzero (P ⴝ .005), and there is a strong correlation in the CCT between the two eyes of each child (r2 ⴝ 0.7).

The cataract patients were younger than the controls or children with pseudophakia or aphakia (Table 1). Because of the age disparity, the eyes of the 25 youngest control subjects (mean age, 5.8 years; mean CCT, 557 ⫾ 35 ␮m [n ⫽ 49 eyes]) were compared with the eyes of subjects with cataracts (mean age, 2.7 years; mean CCT, 566 ⫾ 33 ␮m, as noted above), and no statistically significant difference in mean CCT was noted (P ⫽ .07). The CCT of the 25 youngest normal subjects was similar to that of the all the normal subjects (557 ⫾ 35 ␮m [n ⫽ 49 eyes] vs 552 ⫾ 38 ␮m [n ⫽ 230 eyes], respectively; P ⫽ .4). In addition, linear regression analysis of age vs CCT among our group of 230 control eyes demonstrated no correlation (r2 ⫽ 0.007, data not shown).

TABLE 2. Central Corneal Thickness in Eyes of Children with Cataracts and Normal Controls

All controls Young controls† All cataract‡ Congenital cataract Developmental cataract PFV cataract Microphthalmic cataract

No. of Eyes

Mean CCT (␮m)

Standard Deviation (␮m)

P value*

230 49 35 14 11 5 4

552 557 564 567 562 576 576

38 35 34 39 32 25 25

— — — — .9 .7 .1

CCT ⫽ central corneal thickness; PFV ⫽ persistent fetal vasculature. *P value for the Student t test, two tailed, comparing the CCT of developmental, persistent fetal vasculature, and microphthalmic cataracts with the CCT of congenital cataracts. † The 25 youngest control subjects. ‡ Excludes subjects with Down syndrome, aniridia, and Marfan syndrome.

DISCUSSION WE FOUND THAT WHEN WE EXCLUDED THOSE SUBJECTS

known to have abnormally thin corneas (Down syndrome10 and Marfan syndrome12) and thick corneas (aniridia11) as well as subjects who had undergone glaucoma surgery, the remaining children with cataracts had CCT measurements similar to those of children without cataracts. Furthermore, for children with unilateral cataracts, the CCT of the affected eyes was similar to the CCT of the unaffected eyes. The average CCT of healthy eyes of children 13 days to 17 years of age in our study, 552 ⫾ 38 ␮m, falls within the reported range for the CCT of children of similar age (529 ⫾ 34 ␮m13 to 555 ⫾ 42 ␮m14). Pseudophakic eyes and aphakic eyes of children demonstrated thicker CCT than normal eyes and eyes with cataracts (before surgery). Although the numbers of eyes with specific types of cataracts such as those associated

group, the mean CCT of aphakic eyes with a diagnosis of glaucoma was more than that of aphakic eyes without glaucoma (685 ⫾ 94 ␮m [n ⫽ 32] vs 620 ⫾ 56 ␮m [n ⫽ 25], respectively; P ⬍ .001). The IOP of the aphakic eyes with glaucoma also was more than the IOP of aphakic eyes without glaucoma (25 ⫾ 9 mm Hg [n ⫽ 32] vs 16 ⫾ 4 mm Hg [n ⫽ 25], respectively; P ⬍ .001). Among the aphakic eyes without glaucoma, greater length of time since the cataract extraction correlated with greater CCT (P ⬍ .001; Figure 3). 504

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with persistent fetal vasculature and microphthalmia were small, the CCT measurements among all cataract subgroups were similar. If increased CCT is protective against the development of glaucoma, as the Ocular Hypertension Treatment Study suggests,15 why do up to 45%16 of children with aphakia (and thicker than average CCT6,7) experience glaucoma? It is known that aphakic eyes have thicker CCT than phakic eyes of children.6,7 We also found that greater length of time after cataract extraction correlated with greater CCT in the aphakic eyes not receiving treatment for glaucoma. Although we do not know the preoperative CCT or the actual CCT changes of an individual aphakic eye in this study, it seems nonetheless possible that the duration of aphakic status is related to increased CCT, even in the absence of clinically recognizable corneal edema. The cause of the observed relationship between increased CCT and length of time after cataract removal in our study remains elusive. Hence, Nilforushan and associates recently reported increased CCT in children with aphakia compared with age-matched control eyes, but with similar endothelial cell counts and morphologic features in both groups.17 This recent study similarly lacked knowledge of the CCT at the time of cataract removal in the aphakic eyes. We found that the aphakic eyes with glaucoma had greater mean CCT than the aphakic eyes without glaucoma and that the mean IOP of the aphakic eyes with glaucoma exceeded that of the aphakic eyes without glaucoma in this study. It is possible that the eyes with aphakic glaucoma had a preoperative condition that is associated with both increased CCT and the development of aphakic glaucoma, and thus by analyzing the aphakic eyes with glaucoma we selected for eyes with thick corneas. It is also possible that the presence of elevated IOP further increased the actual CCT in these aphakic eyes, presumably by causing subclinical corneal edema, or by some unknown alternative mechanism. Additionally, topical carbonic anhydrase inhibitors used to treat glaucoma are associated with corneal decompensation in some patients.18 Although no eyes in this study had clinically recognizable corneal edema, 20 of the 32 aphakic eyes with glaucoma were treated with topical carbonic anhydrase inhibitors. This study is limited by a relatively small sample size. We enrolled as many eligible patients as possible, and our post hoc power analysis estimated that we had 80% power to detect a 20-␮m difference between mean CCT of eyes with cataracts vs the control eyes. We cannot exclude the possibility that smaller differences in mean CCT between the groups may exist. However, given published correlations between CCT and measured IOP in normal eyes of children,4,9 a difference of up to 20 ␮m would represent a correction factor of less than 1 mm Hg and therefore would not likely be clinically significant.

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This study also is limited by the age disparity between the subjects with cataracts and the control group. The influence of age on CCT is unclear. Dai and Gunderson found no difference in the CCT of subjects across various age groups from younger than two years to older than 18 years.14 We similarly found no correlation between age and CCT among our normal control eyes. We addressed the issue of age disparity between the diagnostic groups by comparing the youngest normals with the subjects with cataracts and found no difference in CCT. The cataract and control groups also differed in racial make-up, with the normal group more evenly split between Blacks and Whites, whereas most of the cataract group consisted of White children. We and others previously reported thinner CCT in eyes of Black vs those of White children.9,14 Therefore, it is possible that the preponderance of White subjects in the cataract group established bias toward finding a difference in mean CCT between the cataract and normal control groups, and we found no difference. We previously reported that the CCT of unoperated pediatric eyes with and without glaucoma seems to be stable over time.19 The large difference in the CCT of aphakic and pseudophakic eyes vs normal eyes and phakic eyes with cataracts suggests that the increase in CCT (and therefore probably also in overall corneal thickness) likely occurs after surgery. Whether the increased CCT occurs because of endothelial cell damage sustained during cataract removal, or subsequently as a result of the aphakic or pseudophakic state, is unknown. Similarly, it is tempting to postulate that elevated IOP in eyes with glaucoma after cataract removal further injures the corneal endothelial cells in these eyes, resulting in further thickening of the cornea and CCT resulting from subclinical stromal edema. In this sense, the thick cornea of an aphakic child is different from the thick but architecturally normal cornea of an adult with ocular hypertension and may not imply the same prognosis regarding the development of glaucoma. Finally, it is entirely possible that the aphakic eyes measured, and especially those with glaucoma, might have been a sample of eyes that started out with thicker CCT because of microcornea or other structural corneal abnormalities not represented in the present study. Although we did not note thicker CCT in the few eyes with small corneas and cataract in this small study sample, further evaluation and long-term follow-up of CCT in the same eyes before and after cataract removal likely will elucidate this issue further. This study is among the first to describe CCT in the unoperated eyes of children with cataracts. Further study is indicated to determine the influence of different types of cataracts on CCT and the role of CCT in the future development of glaucoma in these children.

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THE AUTHORS INDICATE NO FINANCIAL SUPPORT OR FINANCIAL CONFLICT OF INTEREST. INVOLVED IN CONCEPT AND design (S.F., K.M.); analysis and interpretation of data (S.F., K.M., L.D.); writing the article (K.M., S.F.); critical revision of the article (K.M., S.F., L.D., D.W., L.E.); final approval of the article (S.F.); data collection (L.D., S.F.); provision of materials, patients, or resources (S.F., D.W., L.E.); statistical expertise (S.F., D.W.); obtaining funding (S.F.); literature search (K.M., S.F.); administrative, technical, or logistic support (S.F., L.D.). This study was conducted with the approval of the Duke University Institutional Review Board. Informed consent was provided for all subjects. Informed consent was obtained in accordance with Health Insurance Portability and Accountability Act regulations.

11. Brandt JD, Casuso LA, Budenz DL. Markedly increased central corneal thickness: an unrecognized finding in congenital aniridia. Am J Ophthalmol 2004;137:348 – 350. 12. Sultan G, Baudouin C, Auzerie O, De Saint Jean M, Goldschild M, Pisella PJ. Cornea in Marfan disease: Orbscan and in vivo confocal microscopy analysis. Invest Ophthalmol Vis Sci 2002;43:1757–1764. 13. Doughty MJ, Laiquzzaman M, Muller A, Oblak E, Button NF. Central corneal thickness in European (white) individuals, especially children and the elderly, and assessment of its possible importance in clinical measures of intraocular pressure. Ophthalmic Physiol Opt 2002;22: 491–504. 14. Dai E, Gunderson CA. Pediatric central corneal thickness variation among major ethnic populations. J AAPOS 2006; 10:22–25. 15. Brandt JD, Beiser JA, Kass MA, Gordon MO. Central corneal thickness in the Ocular Hypertension Treatment Study (OHTS). Ophthalmology 2001;108:1779 –1788. 16. Kirwan C, O’Keefe M. Paediatric aphakic glaucoma. Acta Ophthalmol Scand 2006;84:734 –739. 17. Nilforushan N, Falavarjani KG, Razeghinejad MR, Bakhtiari P. Cataract surgery for congenital cataract: endothelial cell characteristics, corneal thickness, and impact on intraocular pressure. J AAPOS 2007;11:159 –161. 18. Konowal A, Morrison JC, Brown SV, et al. Irreversible corneal decompensation in patients treated with topical dorzolamide. Am J Ophthalmol 1999;127:403– 406. 19. Muir KW, Duncan L, Enyedi LB, Stinnett SS, Freedman SF. Central corneal thickness in children: stability over time. Am J Ophthalmol 2006;141:955–957.

REFERENCES 1. Goldmann H. Applanation tonometry. In: Newell F, editor. Glaucoma: transactions of the second conference. New York, New York: Josiah Macy, Jr, Foundation, 1956:167–220. 2. Ehlers N, Hansen FK, Aasved H. Biometric correlations of corneal thickness. Acta Ophthalmol 1975;53:652– 659. 3. Herndon LW, Choudhri SA, Cox T, Damji KF, Shields MB, Allingham RR. Central corneal thickness in normal, glaucomatous, and ocular hypertensive eyes [comment]. Arch Ophthalmol 1997;115:1137–1141. 4. Muir KW, Jin J, Freedman SF. Central corneal thickness and its relationship to intraocular pressure in children. Ophthalmology 2004;111:2220 –2223. 5. Hussein MA, Paysse EA, Bell NP, et al. Corneal thickness in children. Am J Ophthalmol 2004;138:744 –748. 6. Simon JW, O’Malley MR, Gandham SB, Ghaiy R, Zobal-Ratner J, Simmons ST. Central corneal thickness and glaucoma in aphakic and pseudophakic children. J AAPOS 2005;9:326 –329. 7. Simsek T, Mutluay AH, Elgin U, Gursel R, Batman A. Glaucoma and increased central corneal thickness in aphakic and pseudophakic patients after congenital cataract surgery. Br J Ophthalmol 2006;90:1103–1106. 8. Keech RV, Tongue AC, Scott WE. Complications after surgery for congenital and infantile cataracts. Am J Ophthalmol 1989;108:136 –141. 9. Muir KW, Duncan L, Enyedi LB, Freedman SF. Central corneal thickness in children: racial differences (black vs white) and correlation with measured intraocular pressure. J Glaucoma 2006;15:520 –523. 10. Evereklioglu C, Yilmaz K, Bekir NA. Decreased central corneal thickness in children with Down syndrome. J Pediatr Ophthalmol Strabismus 2002;39:274 –277.

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Biosketch Kelly W. Muir is a graduate of the University of North Carolina at Chapel Hill and Duke University Medical School. She completed her ophthalmology residency and glaucoma fellowship at the Duke University Eye Center, where she is currently Chief resident.

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Biosketch Sharon Freedman, MD, is an Associate Professor of Ophthalmology and Pediatrics at the Duke University Eye Center. She specializes in adult/childhood strabismus and in all pediatric eye disorders, particularly childhood glaucoma. Her special interests include congenital and childhood glaucoma, congenital cataracts, retinopathy of prematurity, and torsion associated with macular translocation surgery. Dr Freedman has been consistently honored among the Best Doctors in America, and received Honor Awards from both the American Association of Pediatric Ophthalmology and Strabismus and the American Academy of Ophthalmology.

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