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Comparison of corneal thickness and biomechanical properties between North African and French patients
ARTICLE
Comparison of corneal thickness and biomechanical properties between North African and French patients Sihem Lazreg, MD, Nicolas Mesplie, MD, Delphine Praud, MSc, Cecile Delcourt, PhD, Heykel Kamoun, MD, Mohamed Chahbi, MD, Sandy Leoni-Mesplie, MD, David Smadja, MD, William Trattler, MD, David Touboul, MD, Joseph Colin, MD
PURPOSE: To determine whether corneal thickness and rigidity vary between French and North African refractive surgery candidates. SETTING: Three clinics in North Africa and 1 hospital in France. DESIGN: Cross-sectional study. METHODS: In part 1, the central corneal thickness (CCT) in North African patients and French patients having preoperative examinations was retrospectively compared. In part 2, the biomechanical properties of the corneas in the 2 groups were prospectively compared. Comparisons were performed using the Student t and chi-square tests and multivariate linear and logistic regression. RESULTS: The retrospective study comprised 1662 patients from North Africa and 221 patients from France and the prospective study, 249 and 110, respectively. After adjustment for sex, age, and steepest keratometry, the mean CCT was statistically significantly thinner in North African patients (P<.0001). More than one fourth of North African patients had corneas thinner than 500 mm (28.9% versus 7.7% of French patients). Of patients with thin corneas, the mean corneal resistance factor (CRF) was statistically significantly lower in North African patients (P<.0001); there was no significant difference in corneal hysteresis. This remained true after adjustment for CCT (CCTadjusted difference in CRF between groups: 0.78; range 1.27 to 0.28; PZ.002). CONCLUSION: Corneas were thinner in North African patients than in French patients, and the CRF was different even when CCT was taken into accounted. More research is needed to determine whether these differences are associated with an additional risk for ectasia after laser in situ keratomileusis. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. J Cataract Refract Surg 2013; 39:425–430 Q 2012 ASCRS and ESCRS
Careful evaluation of the preoperative central corneal thickness (CCT) is essential in patients having laser vision correction1–7 because it is important to know whether the cornea is thick enough to create a laser in situ keratomileusis (LASIK) flap and to perform excimer ablation of the stromal bed. There is conflicting evidence on whether the CCT should be considered a risk factor for post-LASIK ectasia. Although a retrospective review of 50 ectasia cases by Randleman et al.8 found that the CCT was an independent risk factor, it was not an independent predictor of post-LASIK ectasia in other studies.9,10 To further Q 2012 ASCRS and ESCRS Published by Elsevier Inc.
complicate the analysis of the impact of CCT on the risk for ectasia, it is known that the CCT differs according to ethnicity.11–16 However, little data are available for patients of North African origin. Findings in only 1 study of 204 patients suggest that patients of North African origin might have thinner corneas.12 The aim of the present study was to compare the CCT in a larger sample of North African patients and French patients and to assess whether the biomechanical properties of the cornea differ according to origin. 0886-3350/$ - see front matter http://dx.doi.org/10.1016/j.jcrs.2012.09.015
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PATIENTS AND METHODS
resistance factor [CRF]) were measured with the Ocular Response Analyzer (Reichert, Inc.). Four measurements were taken; the best waveform score measurement was used.
Study Design and Population Selection The study included patients having a preoperative examination for refractive surgery. In part 1, a retrospective study was performed at 3 centers in North Africa (Blida, Algeria; Casablanca, Morocco; and Tunis, Tunisia) and at a university hospital in France (Bordeaux) to compare the CCT between the regions. The files of all patients who had refractive surgery consultation between January 2009 and November 2009 were reviewed for clinical preoperative measurements (CCT, keratometry, refraction). In part 2 of the study, another population was recruited prospectively to assess the biomechanical properties of the corneas in North African patients and French patients. Patients were recruited prospectively between June 2010 and November 2010 in Blida, Casablanca, and in Bordeaux. Measures of biomechanical properties of the corneas were not available in Tunis. Patients younger than 18 years with keratometry greater than 48.0 diopters (D) or with corneal opacities were excluded. Patients with topography maps consistent with keratoconus or pellucid marginal degeneration (PMD), such as an asymmetric-pattern topography and steepest radial axes above 20 degrees,7 were also excluded.
Clinical Examination In both parts of the study, the evaluation included measurements of the manifest refraction, steepest keratometry, and CCT using the Pentacam Scheimpflug system (Oculus Optikger€ate GmbH) and slitlamp analysis. The Scheimpflug system was used because Barkana et al.17 found that CCT values obtained with the system were similar to those obtained with an ultrasound pachymeter. In the second part of the study, the biomechanical properties of the corneas (corneal hysteresis [CH] and corneal
Submitted: March 30, 2012. Final revision submitted: September 14, 2012. Accepted: September 14, 2012. From Clinique du Dr Lazreg (Lazreg), Blida, Algeria; Department of Ophthalmology (Mesplie, Praud, Leoni-Mesplie, Smadja, Touboul, Colin), University Hospital Pellegrin, University Bordeaux (Mesplie, Leoni-Mesplie, Delcourt, Colin), Institut National de la Sante et de la Recherche Medicale, Centre d’Investigation Clinique–Epidemiologie Clinique 7 (Praud, Delcourt), Institut National de la Sante et de la Recherche Medicale U897 Epidemiologie-Biostatistique, Institut de Sante Publique, d’Epidemiologie et de Developpement (Delcourt), Bordeaux, France; Clinique des Berges du Lac (Kamoun), Tunis, Tunisia; Clinique du Dr Chahbi (Chahbi), Casablanca, Morocco; Center for Excellence in Eye Care (Trattler), Miami, Florida, USA. Supported in part by a grant from l’Union National des Aveugles et Deficients Visuels, France. Corresponding author: Delphine Praud, MSc, Centre Hospitalier Universitaire de Bordeaux, Site Pellegrin, Centre Franc‚ois Xavier Michelet, Service d’Ophtalmologie, Place Amelie Raba Leon, 33076 Bordeaux Cedex, France. E-mail: delphinepraud@gmail. com.
Statistical Analysis Statistical analysis was performed using SAS software (version 9.2, SAS Institute, Inc.). Only the right eye was studied. First, the normality of all data samples was evaluated using the Kolmogorov-Smirnov test. Quantitative demographic and clinical variables were compared between the study groups. If the variables departed from normality, the Wilcoxon test was used. If they had a normal distribution, the Student t test was used. The chi-square test was used to compare proportions of qualitative individual traits between the groups. Correlations were evaluated with the Pearson correlation coefficient (r). In part 1 of the study, because distribution of age and sex was different between North African patients and French patients, comparisons of the steepest keratometry between the 2 groups were adjusted for age and sex using multiple linear regression. Comparisons of CCT between the 2 groups were adjusted for age, sex, and steepest keratometry using multiple linear regressions. Logistic regression models were used to compare categories of CCT between study groups, with adjustment for age and sex. In part 2 of the study, multiple linear regression models, adjusted for CCT, were used to compare the biomechanical properties of the cornea between the 2 groups. Statistical significance was defined as a P value less than 0.05.
RESULTS Part 1 comprised 712 patients from Blida, 657 from Casablanca, 293 from Tunis, and 221 from Bordeaux. Twenty-three patients were excluded for missing values. The North African patients were slightly older than the French patients (Table 1); however, there was no significant difference in age distribution between the regions (Figure 1). There were slightly more women in the North African group (PZ.06) (Table 1). The CCT was thinner in North African patients (P!.0001 after adjustment for age and sex) (Table 1). In most North African patients, the CCT was thinner than 550 mm; in most French patients, it was thicker than 500 mm (Figure 2). The distribution of the CCT was similar in patients from Algeria, Tunisia, and Morocco. The percentage of patients with a CCT thinner than 500 mm was statistically significantly higher in North Africa than in France (P!.0001) (Table 1 and Figure 3). The mean steepest keratometry was statistically significantly higher in North African patients than in French patients (P!.0001) (Table 1). The difference in CCT between North African patients and French patients remained highly significant after further adjustment for steepest keratometry (Table 1). Part 2 of the study comprised 249 patients from North Africa and 110 patients from France. Similar to part 1, the mean CCT was statistically significantly
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Table 1. Distribution of patient characteristics.
Variable Age (y) Mean G SD Range Sex, n (%) Male Female Mean steepest K (D) G SD Mean CCT (mm) G SD CCT, n (%) %500 mm O500 mm
North Africa (n Z 1662)
France (n Z 221)
35.6 G 10.9 16, 90
34.1 G 9.4 18, 59
630 (37.9) 1032 (62.1) 44.0 G 2.2
98 (44.3) 123 (55.7) 42.8 G 1.5
518 G 36
553 G 38
478 (28.9) 1184 (71.1)
17 (7.7) 204 (92.3)
P Value
.03 .06
!.0001* !.0001† !.0001†
Figure 1. Distribution of patient age by study region (N Z 1883).
the CCT and the CH (r Z 0.62, P!.0001) and between the CCT and the CRF (r Z 0.52, P!.0001) in French patients (Table 4).
CCT Z central corneal thickness; K Z keratometry *Adjusted for age and sex † Adjusted for age, sex, and steepest keratometry
DISCUSSION thinner in North African patients (P!.0001) (Table 2). The mean CH was similar in the 2 groups (PZ.28), while the mean CRF was statistically significantly lower in North African patients than in French patients (PZ.0008). Table 3 shows the means of the CH and CRF values in eyes with thin corneas (!500 mm). The mean CRF values remained statistically significantly lower in North African patients in this subgroup of patients (P!.0001), while there was no statistically significant difference in the CH (PZ.51). This remained true after adjustment for CCT. There was a positive correlation between the CCT and the CH (r Z 0.57, P!.0001) and between the CCT and the CRF (r Z 0.65; P!.0001) in North African patients. There was also a positive correlation between
The preoperative evaluation of patients for laser vision correction is critical to ensure that only appropriate candidates are selected. One important test in this setting is the measurement of the CCT, which is performed to determine whether there is sufficient room to create a flap, ablate the bed, and maintain a residual stromal bed of at least 250 mm.8,18 Some surgeons also use a cutoff CCT when deciding whether to offer photorefractive keratectomy or LASIK, with 500 mm being a commonly stated value even though there is scant literature to support this.8,19 However, studies of LASIK in patients with a corneal thickness below 500 mm and normal topographies have not found an increased risk for post-LASIK ectasia.9,10 To complicate matters, the mean CCT can vary significantly between ethnicities.11–16 Thus, the aim of this study was to compare the CCT between 2 ethnic populations as well as to evaluate the biomechanics in these corneas. We found that the CCT was significantly lower in North African patients than in French patients. In more than one fourth of North African patients, the CCT was thinner
Figure 2. Distribution of patients according to CCT by study region (N Z 1883).
Figure 3. Distributions with 95% confidence intervals of patients with a CCT thinner than 500 mm by study region (N Z 1883).
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Table 2. Comparison of pachymetric and biomechanical parameters. Mean G SD Variable
North Africa (n Z 249)
France (n Z 110)
P Value
CCT (mm) CH (mm Hg) CRF (mm Hg)
506 G 36 10.1 G 1.99 9.70 G 2.02
531 G 44 10.32 G 1.77 10.34 G 1.46
!.0001 .28 .0008
CCT Z central corneal thickness; CH Z corneal hysteresis; CRF Z corneal resistance factor
than 500 mm. Moreover, the CRF was also lower in patients from North Africa. The central cornea of North Africa patients was significantly thinner than that of French patients (518 mm versus 553 mm, respectively), with 29% of North African eyes having a corneal thickness of 500 mm or less compared with only 7.7% of French eyes. This difference remained statistically significant after adjustment for sex and age, which was slightly different between samples. This is consistent with findings in a study by Lifshitz et al.12 in which patients of North African origin had thinner corneas. Moreover, in our study, the CCT was similar in patients from the 3 North African countries (Algeria, Morocco, and Tunisia). However, studies have found that the CCT may vary between subpopulations, for example between Asian subpopulations.11 These different studies enable us to conclude the following: the CCT in Japanese (531.7 mm), North Africans (518 mm in our study), and African Americans (521 mm) is thinner than the CCT in whites (550.4 mm), Chinese (555.6 mm), Hispanics (548.1 mm), and Filipinos (550.4 mm).11,12 However, our results should be confirmed by other studies because Gorgun et al.20 showed that the Pentacam device may overestimate the CCT. Even if the mean CCT varies significantly between ethnicities, to our knowledge there is no study that identifies ethnicity as an independent risk factor for post-LASIK ectasia. To determine whether patients from North Africa also had reduced corneal viscoelasticity, Ocular
Response Analyzer testing was performed in a separate group of patients from North Africa and France. The analysis found a CCT of 507 mm in North African eyes and 531 mm in French eyes. The correlations between the CCT and biomechanical measures were significant. In both ethnicities, the CH and CRF values increased with CCT, as is described in the literature.21,22 Despite this major difference in CCT, the CH was similar in the 2 groups. However, the CRF was lower in North African patients than in French patients (9.70 versus 10.34; PZ.0008). The results were similar when the analysis was restricted to thin corneas (CCT !500 mm) and when the CCT was adjusted (PZ.002). Low CH and CRF values as well as a CH value higher than the CRF value may help identify the weakest corneas and might be helpful in keratoconus screening.23–25 In our study, CH values higher than the CRF values were observed in thin North African corneas, suggesting that thin North African corneas could be less viscoelastic than thin French corneas. Our findings have to be confirmed by future studies. Indeed, in our study, it was not possible to adjust the CRF and CH for intraocular pressure (IOP) because of a defect in data collection at 1 center. Touboul et al.23 found that IOP values were correlated with biomechanical properties. Even though we did not study patients with glaucoma, the IOP values could be a confounder. Nevertheless, patients included in the present study were relatively young, with low expected rates of ocular hypertension.26,27 Moreover, all patients with keratoconus and PMD were excluded; however, the number of patients excluded in both groups was not collected. This is a possible limitation of our study because it may have induced a systematic difference between groups. Studies should also be performed to specify in more detail the difference in biomechanical changes between ethnic groups, in particular with the new Ocular Response Analyzer software, which appears to include more sophisticated parameters to detect biomechanical changes. However, to our knowledge, there are no other published studies comparing the corneal biomechanical properties of the ethnic groups we evaluated.
Table 3. Comparison of CH and CRF in patients with a CCT thinner than 500 mm. Mean G SD Variable CH (mm Hg) CRF (mm Hg)
North Africa (n Z 123)
France (n Z 45)
P Value
9.17 G 1.68 8.65 G 1.55
9.36 G 1.55 9.71 G 1.43
.51 !.0001
CCT Z central corneal thickness; CH Z corneal hysteresis; CRF Z corneal resistance factor
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CCT-Adjusted Difference Between Groups (Range) 0.07 ( 0.48, 0.62) 0.78 ( 1.27, 0.28)
P Value .80 .002
CORNEAL THICKNESS AND BIOMECHANICAL PROPERTIES OF NORTH AFRICAN AND FRENCH PATIENTS
Table 4. Correlation between CH and CRF and CCT. Correlation with CCT Variable
In North Africa
In France
CH (mm Hg) CRF (mm Hg)
0.57 (P!.0001) 0.65 (P!.0001)
0.62 (P!.0001) 0.52 (P!.0001)
CCT Z central corneal thickness; CH Z corneal hysteresis; CRF Z corneal resistance factor
In conclusion, the corneas were significantly thinner in North African patients than in French patients, and after adjustment for CCT, thin North African corneas had a lower CRF, a measure of overall elastic resistance of the cornea, than thin French corneas. Further research in this area should be performed to determine whether these differences are associated with an additional risk for post-LASIK ectasia. However, these results suggest caution before performing LASIK on thin North African corneas. WHAT WAS KNOWN Central corneal thickness is an important parameter in the preoperative examination for refractive surgery. It is known that the CCT is different according to ethnicity. Only 1 study suggests that patients of North African origin might have thinner corneas. WHAT THIS PAPER ADDS Corneas were thinner in North African patients than in French patients. After adjustment for CCT, the CRF, a measure of the overall elastic resistance of the cornea, was lower in North African patients than in French patients. More research is needed to determine whether these differences are associated with an additional risk for postLASIK ectasia.
REFERENCES 1. Seiler T, Koufala K, Richter G. Iatrogenic keratectasia after laser in situ keratomileusis. J Refract Surg 1998; 14:312–317 2. Seiler T, Quurke AW. Iatrogenic keratectasia after LASIK in a case of forme fruste keratoconus. J Cataract Refract Surg 1998; 24:1007–1009 3. Amoils SP, Deist MB, Gous P, Amoils PM. Iatrogenic keratectasia after laser in situ keratomileusis for less than 4.0 to 7.0 diopters of myopia. J Cataract Refract Surg 2000; 26:967–977 4. Comaish IF, Lawless MA. Progressive post-LASIK keratectasia; biomechanical instability or chronic disease process? J Cataract Refract Surg 2002; 28:2206–2213 sio R Jr, Wilson SE. Early pellucid marginal corneal de5. Ambro generation; case reports of two refractive surgery candidates. Cornea 2002; 21:114–117
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6. Binder PS, Lindstrom RL, Stulting RD, Donnenfeld E, Wu H, McDonnell P, Rabinowitz Y. Keratoconus and corneal ectasia after LASIK. J Refract Surg 2005; 21:749–752 7. Rabinowitz YS. Keratoconus. Surv Ophthalmol 1998; 42:297– 319. Available at: http://www.keratoconus.com/resources/ MajorCReview-Keratoconus.pdf. Accessed September 29, 2012 8. Randleman JB, Trattler WB, Stulting RD. Validation of the Ectasia Risk Score System for preoperative laser in situ keratomileusis screening. Am J Ophthalmol 2008; 145:813–818 9. Binder PS, Trattler WB. Evaluation of a risk factor scoring system for corneal ectasia after LASIK in eyes with normal topography. J Refract Surg 2010; 26:241–250 10. Caster AI, Friess DW, Potvin RJ. Absence of keratectasia after LASIK in eyes with preoperative central corneal thickness of 450 to 500 microns. J Refract Surg 2007; 23:782–788 11. Aghaian E, Choe JE, Lin S, Stamper RL. Central corneal thickness of Caucasians, Chinese, Hispanics, Filipinos, African Americans, and Japanese in a glaucoma clinic. Ophthalmology 2004; 111:2211–2219 12. Lifshitz T, Levy J, Rosen S, Belfair N, Levinger S. Central corneal thickness and its relationship to the patient’s origin. Eye 2006; 20:460–465. Available at: http://www.nature.com/eye/ journal/v20/n4/pdf/6701911a.pdf. Accessed September 29, 2012 13. Hashemi H, Yazdani K, Mehravaran S, KhabazKhoob M, Mohammad K, Parsafar H, Fotouhi A. Corneal thickness in a population-based, cross-sectional study: the Tehran Eye Study. Cornea 2009; 28:395–400 14. Nemesure B, Wu S-Y, Hennis A, Leske MC, for the Barbados Eye Study Group. Corneal thickness and intraocular pressure in the Barbados Eye Studies. Arch Ophthalmol 2003; 121:240–244. Available at: http://archopht.jamanetwork.com/ data/Journals/OPHTH/9900/EEB20002.pdf. Accessed September 29, 2012 15. La Rosa FA, Gross RL, Orengo-Nania S. Central corneal thickness of Caucasians and African Americans in glaucomatous and nonglaucomatous populations. Arch Ophthalmol 2001; 119:23– 27 16. Semes L, Shaikh A, McGwin G, Bartlett JD. The relationship among race, iris color, central corneal thickness, and intraocular pressure. Optom Vis Sci 2006; 83:512–515 17. Barkana Y, Gerber Y, Elbaz U, Schwartz S, Ken-Dror G, Avni I, Zadok D. Central corneal thickness measurement with the Pentacam Scheimpflug system, optical low-coherence reflectometry pachymeter, and ultrasound pachymetry. J Cataract Refract Surg 2005; 31:1729–1735 18. Martin R, Rachidi H. Stability of posterior corneal elevation one year after myopic laser in situ keratomileusis. Clin Exp Optom 2012; 95:177–186 19. Randleman JB, Woodward M, Lynn MJ, Stulting RD. Risk assessment for ectasia after corneal refractive surgery. Ophthalmology 2008; 115:37–50 20. Gorgun E, Kucumen RB, Yenerel NM. Influence of intrastromal corneal ring segment implantation on corneal biomechanical parameters in keratoconic eyes. Jpn J Ophthalmol 2011; 55:467–471 21. Leite MT, Alencar LM, Gore C, Weinreb RN, Sample PA, Zangwill LM, Medeiros FA. Comparison of corneal biomechanical properties between healthy blacks and whites using the Ocular Response Analyzer. Am J Ophthalmol 2010; 150:163–168 22. Lau W, Pye D. A clinical description of Ocular Response Analyzer measurements. Invest Ophthalmol Vis Sci 2011; 52:2911–2916. Available at: http://www.iovs.org/content/52/6/ 2911.full.pdf. Accessed September 29, 2012
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rautret J, Garra C, Maurice-Tison S, 23. Touboul D, Roberts C, Ke Saubusse E, Colin J. Correlations between corneal hysteresis, intraocular pressure, and corneal central pachymetry. J Cataract Refract Surg 2008; 34:616–622 nard A, Mahmoud AM, Gallois A, Colin J, 24. Touboul D, Be Roberts CJ. Early biomechanical keratoconus pattern measured with an ocular response analyzer: curve analysis. J Cataract Refract Surg 2011; 37:2144–2150 25. Schweitzer C, Roberts CJ, Mahmoud AM, Colin J, MauriceTison S, Kerautret J. Screening of forme fruste keratoconus with the Ocular Response Analyzer. Invest Ophthalmol Vis Sci 2010; 51:2403–2410. Available at: http://www.iovs. org/content/51/5/2403.full.pdf. Accessed September 29, 2012
26. Bonomi L, Marchini G, Marraffa M, Bernardi P, De Franco I, Perfetti S, Varotto A, Tenna V. Prevalence of glaucoma and intraocular pressure distribution in a defined population; the EgnaNeumarkt Study. Ophthalmology 1998; 105:209–215 27. Delcourt C, Bron A, Baudouin C, Denis P, Nordmann J-P, Renard J-P, Rouland J-F, Sellem E, Stephan M, Levrat F, valence et description du traitement par hypotoniSolesse A. Pre sants pour glaucome et hypertonie oculaire en France [Prevalence and description of treatment with intraocular pressure-lowering topical medications in continental France]. J Fr Ophtalmol 2006; 29:1098–1106. Available at: http://www.em-consulte.com/ ajax/modulePdfFlashArticle/article/113150/pdf/prevalence-etdescription-du-traitement-par-hypoto. Accessed September 29, 2012
J CATARACT REFRACT SURG - VOL 39, MARCH 2013
Comparison of corneal thickness and biomechanical properties between North African and French patients Sihem Lazreg, MD, Nicolas Mesplie, MD, Delphine Praud, MSc, Cecile Delcourt, PhD, Heykel Kamoun, MD, Mohamed Chahbi, MD, Sandy Leoni-Mesplie, MD, David Smadja, MD, William Trattler, MD, David Touboul, MD, Joseph Colin, MD
PURPOSE: To determine whether corneal thickness and rigidity vary between French and North African refractive surgery candidates. SETTING: Three clinics in North Africa and 1 hospital in France. DESIGN: Cross-sectional study. METHODS: In part 1, the central corneal thickness (CCT) in North African patients and French patients having preoperative examinations was retrospectively compared. In part 2, the biomechanical properties of the corneas in the 2 groups were prospectively compared. Comparisons were performed using the Student t and chi-square tests and multivariate linear and logistic regression. RESULTS: The retrospective study comprised 1662 patients from North Africa and 221 patients from France and the prospective study, 249 and 110, respectively. After adjustment for sex, age, and steepest keratometry, the mean CCT was statistically significantly thinner in North African patients (P<.0001). More than one fourth of North African patients had corneas thinner than 500 mm (28.9% versus 7.7% of French patients). Of patients with thin corneas, the mean corneal resistance factor (CRF) was statistically significantly lower in North African patients (P<.0001); there was no significant difference in corneal hysteresis. This remained true after adjustment for CCT (CCTadjusted difference in CRF between groups: 0.78; range 1.27 to 0.28; PZ.002). CONCLUSION: Corneas were thinner in North African patients than in French patients, and the CRF was different even when CCT was taken into accounted. More research is needed to determine whether these differences are associated with an additional risk for ectasia after laser in situ keratomileusis. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. J Cataract Refract Surg 2013; 39:425–430 Q 2012 ASCRS and ESCRS
Careful evaluation of the preoperative central corneal thickness (CCT) is essential in patients having laser vision correction1–7 because it is important to know whether the cornea is thick enough to create a laser in situ keratomileusis (LASIK) flap and to perform excimer ablation of the stromal bed. There is conflicting evidence on whether the CCT should be considered a risk factor for post-LASIK ectasia. Although a retrospective review of 50 ectasia cases by Randleman et al.8 found that the CCT was an independent risk factor, it was not an independent predictor of post-LASIK ectasia in other studies.9,10 To further Q 2012 ASCRS and ESCRS Published by Elsevier Inc.
complicate the analysis of the impact of CCT on the risk for ectasia, it is known that the CCT differs according to ethnicity.11–16 However, little data are available for patients of North African origin. Findings in only 1 study of 204 patients suggest that patients of North African origin might have thinner corneas.12 The aim of the present study was to compare the CCT in a larger sample of North African patients and French patients and to assess whether the biomechanical properties of the cornea differ according to origin. 0886-3350/$ - see front matter http://dx.doi.org/10.1016/j.jcrs.2012.09.015
425
426
CORNEAL THICKNESS AND BIOMECHANICAL PROPERTIES OF NORTH AFRICAN AND FRENCH PATIENTS
PATIENTS AND METHODS
resistance factor [CRF]) were measured with the Ocular Response Analyzer (Reichert, Inc.). Four measurements were taken; the best waveform score measurement was used.
Study Design and Population Selection The study included patients having a preoperative examination for refractive surgery. In part 1, a retrospective study was performed at 3 centers in North Africa (Blida, Algeria; Casablanca, Morocco; and Tunis, Tunisia) and at a university hospital in France (Bordeaux) to compare the CCT between the regions. The files of all patients who had refractive surgery consultation between January 2009 and November 2009 were reviewed for clinical preoperative measurements (CCT, keratometry, refraction). In part 2 of the study, another population was recruited prospectively to assess the biomechanical properties of the corneas in North African patients and French patients. Patients were recruited prospectively between June 2010 and November 2010 in Blida, Casablanca, and in Bordeaux. Measures of biomechanical properties of the corneas were not available in Tunis. Patients younger than 18 years with keratometry greater than 48.0 diopters (D) or with corneal opacities were excluded. Patients with topography maps consistent with keratoconus or pellucid marginal degeneration (PMD), such as an asymmetric-pattern topography and steepest radial axes above 20 degrees,7 were also excluded.
Clinical Examination In both parts of the study, the evaluation included measurements of the manifest refraction, steepest keratometry, and CCT using the Pentacam Scheimpflug system (Oculus Optikger€ate GmbH) and slitlamp analysis. The Scheimpflug system was used because Barkana et al.17 found that CCT values obtained with the system were similar to those obtained with an ultrasound pachymeter. In the second part of the study, the biomechanical properties of the corneas (corneal hysteresis [CH] and corneal
Submitted: March 30, 2012. Final revision submitted: September 14, 2012. Accepted: September 14, 2012. From Clinique du Dr Lazreg (Lazreg), Blida, Algeria; Department of Ophthalmology (Mesplie, Praud, Leoni-Mesplie, Smadja, Touboul, Colin), University Hospital Pellegrin, University Bordeaux (Mesplie, Leoni-Mesplie, Delcourt, Colin), Institut National de la Sante et de la Recherche Medicale, Centre d’Investigation Clinique–Epidemiologie Clinique 7 (Praud, Delcourt), Institut National de la Sante et de la Recherche Medicale U897 Epidemiologie-Biostatistique, Institut de Sante Publique, d’Epidemiologie et de Developpement (Delcourt), Bordeaux, France; Clinique des Berges du Lac (Kamoun), Tunis, Tunisia; Clinique du Dr Chahbi (Chahbi), Casablanca, Morocco; Center for Excellence in Eye Care (Trattler), Miami, Florida, USA. Supported in part by a grant from l’Union National des Aveugles et Deficients Visuels, France. Corresponding author: Delphine Praud, MSc, Centre Hospitalier Universitaire de Bordeaux, Site Pellegrin, Centre Franc‚ois Xavier Michelet, Service d’Ophtalmologie, Place Amelie Raba Leon, 33076 Bordeaux Cedex, France. E-mail: delphinepraud@gmail. com.
Statistical Analysis Statistical analysis was performed using SAS software (version 9.2, SAS Institute, Inc.). Only the right eye was studied. First, the normality of all data samples was evaluated using the Kolmogorov-Smirnov test. Quantitative demographic and clinical variables were compared between the study groups. If the variables departed from normality, the Wilcoxon test was used. If they had a normal distribution, the Student t test was used. The chi-square test was used to compare proportions of qualitative individual traits between the groups. Correlations were evaluated with the Pearson correlation coefficient (r). In part 1 of the study, because distribution of age and sex was different between North African patients and French patients, comparisons of the steepest keratometry between the 2 groups were adjusted for age and sex using multiple linear regression. Comparisons of CCT between the 2 groups were adjusted for age, sex, and steepest keratometry using multiple linear regressions. Logistic regression models were used to compare categories of CCT between study groups, with adjustment for age and sex. In part 2 of the study, multiple linear regression models, adjusted for CCT, were used to compare the biomechanical properties of the cornea between the 2 groups. Statistical significance was defined as a P value less than 0.05.
RESULTS Part 1 comprised 712 patients from Blida, 657 from Casablanca, 293 from Tunis, and 221 from Bordeaux. Twenty-three patients were excluded for missing values. The North African patients were slightly older than the French patients (Table 1); however, there was no significant difference in age distribution between the regions (Figure 1). There were slightly more women in the North African group (PZ.06) (Table 1). The CCT was thinner in North African patients (P!.0001 after adjustment for age and sex) (Table 1). In most North African patients, the CCT was thinner than 550 mm; in most French patients, it was thicker than 500 mm (Figure 2). The distribution of the CCT was similar in patients from Algeria, Tunisia, and Morocco. The percentage of patients with a CCT thinner than 500 mm was statistically significantly higher in North Africa than in France (P!.0001) (Table 1 and Figure 3). The mean steepest keratometry was statistically significantly higher in North African patients than in French patients (P!.0001) (Table 1). The difference in CCT between North African patients and French patients remained highly significant after further adjustment for steepest keratometry (Table 1). Part 2 of the study comprised 249 patients from North Africa and 110 patients from France. Similar to part 1, the mean CCT was statistically significantly
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Table 1. Distribution of patient characteristics.
Variable Age (y) Mean G SD Range Sex, n (%) Male Female Mean steepest K (D) G SD Mean CCT (mm) G SD CCT, n (%) %500 mm O500 mm
North Africa (n Z 1662)
France (n Z 221)
35.6 G 10.9 16, 90
34.1 G 9.4 18, 59
630 (37.9) 1032 (62.1) 44.0 G 2.2
98 (44.3) 123 (55.7) 42.8 G 1.5
518 G 36
553 G 38
478 (28.9) 1184 (71.1)
17 (7.7) 204 (92.3)
P Value
.03 .06
!.0001* !.0001† !.0001†
Figure 1. Distribution of patient age by study region (N Z 1883).
the CCT and the CH (r Z 0.62, P!.0001) and between the CCT and the CRF (r Z 0.52, P!.0001) in French patients (Table 4).
CCT Z central corneal thickness; K Z keratometry *Adjusted for age and sex † Adjusted for age, sex, and steepest keratometry
DISCUSSION thinner in North African patients (P!.0001) (Table 2). The mean CH was similar in the 2 groups (PZ.28), while the mean CRF was statistically significantly lower in North African patients than in French patients (PZ.0008). Table 3 shows the means of the CH and CRF values in eyes with thin corneas (!500 mm). The mean CRF values remained statistically significantly lower in North African patients in this subgroup of patients (P!.0001), while there was no statistically significant difference in the CH (PZ.51). This remained true after adjustment for CCT. There was a positive correlation between the CCT and the CH (r Z 0.57, P!.0001) and between the CCT and the CRF (r Z 0.65; P!.0001) in North African patients. There was also a positive correlation between
The preoperative evaluation of patients for laser vision correction is critical to ensure that only appropriate candidates are selected. One important test in this setting is the measurement of the CCT, which is performed to determine whether there is sufficient room to create a flap, ablate the bed, and maintain a residual stromal bed of at least 250 mm.8,18 Some surgeons also use a cutoff CCT when deciding whether to offer photorefractive keratectomy or LASIK, with 500 mm being a commonly stated value even though there is scant literature to support this.8,19 However, studies of LASIK in patients with a corneal thickness below 500 mm and normal topographies have not found an increased risk for post-LASIK ectasia.9,10 To complicate matters, the mean CCT can vary significantly between ethnicities.11–16 Thus, the aim of this study was to compare the CCT between 2 ethnic populations as well as to evaluate the biomechanics in these corneas. We found that the CCT was significantly lower in North African patients than in French patients. In more than one fourth of North African patients, the CCT was thinner
Figure 2. Distribution of patients according to CCT by study region (N Z 1883).
Figure 3. Distributions with 95% confidence intervals of patients with a CCT thinner than 500 mm by study region (N Z 1883).
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Table 2. Comparison of pachymetric and biomechanical parameters. Mean G SD Variable
North Africa (n Z 249)
France (n Z 110)
P Value
CCT (mm) CH (mm Hg) CRF (mm Hg)
506 G 36 10.1 G 1.99 9.70 G 2.02
531 G 44 10.32 G 1.77 10.34 G 1.46
!.0001 .28 .0008
CCT Z central corneal thickness; CH Z corneal hysteresis; CRF Z corneal resistance factor
than 500 mm. Moreover, the CRF was also lower in patients from North Africa. The central cornea of North Africa patients was significantly thinner than that of French patients (518 mm versus 553 mm, respectively), with 29% of North African eyes having a corneal thickness of 500 mm or less compared with only 7.7% of French eyes. This difference remained statistically significant after adjustment for sex and age, which was slightly different between samples. This is consistent with findings in a study by Lifshitz et al.12 in which patients of North African origin had thinner corneas. Moreover, in our study, the CCT was similar in patients from the 3 North African countries (Algeria, Morocco, and Tunisia). However, studies have found that the CCT may vary between subpopulations, for example between Asian subpopulations.11 These different studies enable us to conclude the following: the CCT in Japanese (531.7 mm), North Africans (518 mm in our study), and African Americans (521 mm) is thinner than the CCT in whites (550.4 mm), Chinese (555.6 mm), Hispanics (548.1 mm), and Filipinos (550.4 mm).11,12 However, our results should be confirmed by other studies because Gorgun et al.20 showed that the Pentacam device may overestimate the CCT. Even if the mean CCT varies significantly between ethnicities, to our knowledge there is no study that identifies ethnicity as an independent risk factor for post-LASIK ectasia. To determine whether patients from North Africa also had reduced corneal viscoelasticity, Ocular
Response Analyzer testing was performed in a separate group of patients from North Africa and France. The analysis found a CCT of 507 mm in North African eyes and 531 mm in French eyes. The correlations between the CCT and biomechanical measures were significant. In both ethnicities, the CH and CRF values increased with CCT, as is described in the literature.21,22 Despite this major difference in CCT, the CH was similar in the 2 groups. However, the CRF was lower in North African patients than in French patients (9.70 versus 10.34; PZ.0008). The results were similar when the analysis was restricted to thin corneas (CCT !500 mm) and when the CCT was adjusted (PZ.002). Low CH and CRF values as well as a CH value higher than the CRF value may help identify the weakest corneas and might be helpful in keratoconus screening.23–25 In our study, CH values higher than the CRF values were observed in thin North African corneas, suggesting that thin North African corneas could be less viscoelastic than thin French corneas. Our findings have to be confirmed by future studies. Indeed, in our study, it was not possible to adjust the CRF and CH for intraocular pressure (IOP) because of a defect in data collection at 1 center. Touboul et al.23 found that IOP values were correlated with biomechanical properties. Even though we did not study patients with glaucoma, the IOP values could be a confounder. Nevertheless, patients included in the present study were relatively young, with low expected rates of ocular hypertension.26,27 Moreover, all patients with keratoconus and PMD were excluded; however, the number of patients excluded in both groups was not collected. This is a possible limitation of our study because it may have induced a systematic difference between groups. Studies should also be performed to specify in more detail the difference in biomechanical changes between ethnic groups, in particular with the new Ocular Response Analyzer software, which appears to include more sophisticated parameters to detect biomechanical changes. However, to our knowledge, there are no other published studies comparing the corneal biomechanical properties of the ethnic groups we evaluated.
Table 3. Comparison of CH and CRF in patients with a CCT thinner than 500 mm. Mean G SD Variable CH (mm Hg) CRF (mm Hg)
North Africa (n Z 123)
France (n Z 45)
P Value
9.17 G 1.68 8.65 G 1.55
9.36 G 1.55 9.71 G 1.43
.51 !.0001
CCT Z central corneal thickness; CH Z corneal hysteresis; CRF Z corneal resistance factor
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CCT-Adjusted Difference Between Groups (Range) 0.07 ( 0.48, 0.62) 0.78 ( 1.27, 0.28)
P Value .80 .002
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Table 4. Correlation between CH and CRF and CCT. Correlation with CCT Variable
In North Africa
In France
CH (mm Hg) CRF (mm Hg)
0.57 (P!.0001) 0.65 (P!.0001)
0.62 (P!.0001) 0.52 (P!.0001)
CCT Z central corneal thickness; CH Z corneal hysteresis; CRF Z corneal resistance factor
In conclusion, the corneas were significantly thinner in North African patients than in French patients, and after adjustment for CCT, thin North African corneas had a lower CRF, a measure of overall elastic resistance of the cornea, than thin French corneas. Further research in this area should be performed to determine whether these differences are associated with an additional risk for post-LASIK ectasia. However, these results suggest caution before performing LASIK on thin North African corneas. WHAT WAS KNOWN Central corneal thickness is an important parameter in the preoperative examination for refractive surgery. It is known that the CCT is different according to ethnicity. Only 1 study suggests that patients of North African origin might have thinner corneas. WHAT THIS PAPER ADDS Corneas were thinner in North African patients than in French patients. After adjustment for CCT, the CRF, a measure of the overall elastic resistance of the cornea, was lower in North African patients than in French patients. More research is needed to determine whether these differences are associated with an additional risk for postLASIK ectasia.
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