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Corneal resistance factor and corneal hysteresis in a 6- to 18-year-old population

Hashemi, Hassan MD; Jafarzadehpur, Ebrahim PhD; Mehravaran, Shiva MD; Yekta, Abbasali PhD; Ostadimoghaddam, Hadi PhD; Norouzirad, Reza MSc; Khabazkhoob, Mehdi MSC*

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Journal of Cataract & Refractive Surgery: September 2014 - Volume 40 - Issue 9 - p 1446-1453
doi: 10.1016/j.jcrs.2013.12.019
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Abstract

Corneal hysteresis (CH) and the corneal resistance factor (CRF) are clinical metrics of corneal biomechanical properties that are measured by a dynamic bidirectional applanation device (Ocular Response Analyzer, Reichert Ophthalmic Instruments).1–3 Corneal hysteresis represents a measure of viscous damping in the corneal tissue, and the CRF is the cumulative effects of the viscous and elastic resistance of the cornea.1,2 The relationships of these indices with diseases such as keratoconus,4 Fuchs corneal dystrophy,5 and glaucoma6 have brought them to the attention of ophthalmic researchers in the past decade.

The values of corneal biomechanical properties before refractive surgery can affect the outcomes of surgery.7 Some studies8–10 have evaluated the normal ranges of these indices in different samples. In most studies, the mean CH and the CRF in normal eyes range between 10 mm Hg and 11 mm Hg,8–10 and the reported range in normal populations is between 8 mm Hg and 16 mm Hg.11 Indices found to be correlated with CH and the CRF include the central corneal thickness (CCT) and intraocular pressure (IOP). A relationship between CH and myopia has been observed.12 Some studies found that CH decreases in diabetic patients as a result of changes in corneal collagen. Although we know that the mean CRF and CH values decrease with age, few studies have described their normal range and the changes in children and adolescents, and most of those in the literature sampled myopic children.12 The only studies on average CH and CRF values in children are from China and Singapore.9,10 These geographic areas are known to have a high prevalence of myopia; thus, the results in these studies are not applicable to all areas of the world. Due to the ethnic, geographic, and genetic changes in Ocular Response Analyzer measurements, knowledge of the average and normal ranges of CH and CRF values in children and adolescents in each geographic area and ethnicity can be beneficial.

In this study, we present the normal values and ranges of CH and the CRF in a 6- to 18-year-old Iranian population. We also explored the relationship between corneal biomechanical properties and ocular biometrics.

Subjects and methods

The target population in this study was students in Dezful, a city in southwest Iran. Written informed consent for all steps of the study was obtained from all students and their parents or guardians. The Research and Ethics Committee of Vice Chancellor for Research of Tehran University of Medical Sciences approved the study.

Sampling was performed using a multistage, stratified, cluster sampling approach. In the current educational system in Iran, there are 6 grades in elementary school, 2 in middle school, and 4 in high school; coeducation is not available at any of these levels. Thus, first, from the boys’ and girls’ schools in Dezful, 1 elementary school, 1 middle school, and 1 high school were chosen. In each school (stratum), 1 class from each grade (cluster) was randomly chosen, and all students in that class were approached. On the examination day, after settling in a suitable space, students with a signed informed consent were enrolled in the study. When a given grade (cluster) had more than 1 class, 1 was selected by random and students in that class were examined consecutively. Each student first had an interview and then was examined.

Examinations

In all cases, examinations included biometry, noncycloplegic refraction, and corneal biomechanical properties. In all cases, first the right eye and then the left eye were examined to avoid confusion. Biometry was performed using Lenstar/Biograph system (Wavelight AG) by an optometrist, who checked the measurements before recording them to ensure there were no errors. In cases of error, artificial tears were instilled and biometry was repeated 5 minutes later. Next, noncycloplegic objective refraction was performed using the KR-8000 autorefractor (Topcon Corp.). Finally, corneal biomechanical properties were measured using the Ocular Response Analyzer dynamic bidirectional applanation device (version 2.04 software). After the height of the instrument table was adjusted, the student was instructed to lean forward with the chin inward and placed very close to the device, rest the forehead on the forehead pad, and remain fixated on the green light inside the device tube. The best measurement is achieved when the green light in the middle is surrounded by 3 red lights. In this situation, the student was asked to blink a couple of times and then resume focusing on the green light. Next, the operator clicked the measurement button on the device, generating an air puff. At this point, the measurements were taken.

Only good-quality readings of the dynamic bidirectional applanation device readings were recorded. Three high-quality measurements were performed in each eye. To minimize potential confounding effects related to diurnal variation in pressure or hydration, all examinations were performed between 10 am and 4 pm.

Statistical Analysis

Each index was measured 3 times, and the average reading was used for analysis. The mean and 95% confidence interval (CI) were determined to describe CH, the CRF, the area of peak 1 (p1 area), and the area of peak 2 (p2 area). The sampling method and clusters were taken into account in calculating standard errors and CIs. Independent variables included age, sex, axial length (AL) of the eye, CCT, mean keratometry (K), lens thickness, pupil diameter, and corneal diameter. Simple and multiple linear regression models were used to examine the relationship between the CH and CRF values and independent variables.

Results

Of the 864 selected students, 683 participated in the study (79.1% response rate). The mean age of the students was 12 years ± 3.4 (SD) (range 6 to 18 years); 377 of them (55.2%) were boys.

Figure 1 shows the distribution of CRF; according to the Kolmogorov-Smirnov test, the distribution of CRF was different from normal (P=.028). Table 1 shows the 5th to 99th percentiles of CRF; 34 students (5%) had a CRF of 8.7 mm Hg or less, and the 95th percentile of the index was 15.2 mm Hg. The normal range for CRF, based on the mean ± (2 × SD), was 8.19 mm Hg to 15.28 mm Hg. Table 2 shows the mean and 95% CIs of the CRF by age and sex. The mean CRF was significantly higher in girls (P=.003). There was no significant difference in CRF between age groups (P=.169), even after adjusting for sex (P=.173) (Table 2).

Figure 1
Figure 1:
Distribution of CRF and CH.
Table 1
Table 1:
Percentiles of CRF and CH.
Table 2
Table 2:
Mean and 95% CIs for the CRF and CH in 6- to 18-year-old students in Dezful.

Figure 1 also shows the distribution of CH. According to the Kolmogorov-Smirnov test, the distribution of CH was not significantly different from normal (P=.070). Thirty-four students (5%) had CH of 8.5 mm Hg or less, and the 95th and 99th percentiles for this index were 14.5 mm Hg and 16 mm Hg, respectively. The normal range in all eyes was 7.67 to 15.31 mm Hg. The difference in CH between boys and girls was not statistically significant (P=.383), and CH was not significantly correlated with age (P=.315).

Table 3 shows results of the simple and multiple linear regression models. In the simple regression model, the relationship between CRF and AL was inverse; that is, every millimeter decrease in AL was associated with a 0.295 mm Hg increase in the CRF (P=.010). Also, the CRF was directly associated with CCT (P<.001) (Figure 2), keratometry (P=.043), and corneal diameter, with borderline significance for the latter (P=.053). The relationships with anterior chamber depth, lens thickness, and pupil diameter were not statistically significant (Table 3). Corneal hysteresis showed a stronger association with AL than the CRF; every millimeter increase in AL was associated with a 0.414 mm Hg decrease in CH (P<.001). There were direct associations between CH and the CCT (Figure 3) and mean K, and every millimeter decrease in corneal diameter was associated with a 0.446 mm Hg reduction in CH (P=.009). According to results of the multiple linear regression (Table 3), after including the variables of age, sex, AL, mean K, CCT, pupil diameter, and corneal diameter in the model, female sex (β coefficient = −0.488), a higher CCT (β coefficient = 0.034), and a higher mean K value (β coefficient = 0.157) were significantly correlated with increased CRF. Also, there was a significant correlation between CH and increased CCT (β coefficient = 0.025). There was also a significant correlation between the mean K value (β coefficient = 0.11) and a shorter AL (β coefficient = −0.303), and subsequently with CH.

Figure 2
Figure 2:
Correlation between CRF and CCT.
Figure 3
Figure 3:
Correlation between CH and CCT.
Table 3
Table 3:
Results of simple and multiple linear regression.

The mean difference between CH and CRF values (CH − CRF) was −0.25 mm Hg (95% CI, −0.33 to −0.17); the difference was −0.52 mm Hg (95% CI, −0.62 to −0.42) in girls and −0.021 mm Hg (95% CI, −0.14 to 0.096) in boys. The difference in this index between boys and girls was statistically significant (P<.001); however, it showed no statistically significant association with age (P=.279).

The mean p1 area was 3072.0 (95% CI, 2950.3-3193.7) and the mean p2 area, 2420.0 (95% CI, 2322.3-2517.6). Figure 4 shows the distributions of these variables in the study population. The mean p1 area (P=.369) and p2 area (P=.107) were not statistically significantly different between boys and girls, even after adjusting for age. The p1 area significantly decreased with age; after adjusting for sex, each year increase in age was associated with a 42-unit decrease in the p1 area (P=.003). The relationship between the p2 area and age was not statistically significant (P=.836).

Figure 4
Figure 4:
Distribution of p1 area and p2 area (p1area = area of peak 1; p2area = area of peak 1).

Discussion

In the present study, we report the mean and normal range of corneal biomechanical values (CH and CRF) in an Iranian population for the first time. Similar studies give a detailed description of these indices in different populations.13–24 Results in our study showed that the mean CRF was 11.74 mm Hg and its normal range was from 8.19 to 15.28 mm Hg. The mean CH in this study was 11.49 mm Hg with a normal range from 7.67 to 15.31 mm Hg. Table 4 is a summary of results in studies of other populations.9–12,14–20,25 As seen, the mean corneal biomechanical properties in some East Asian countries were lower than in our study.

Table 4
Table 4:
Results in other studies.

We compared age groups in other studies that were closer to those in our study sample. Our Iranian students had higher CH and CRF values than the values in a study of Chinese students, although the findings in the Singapore study were not very different from our findings in Iran (Table 4). Important factors can be responsible for variations between countries. Some reports suggest that race is a factor. For example, Leite et al.19 found that African American people have lower CH and CRF values than white people. Detry-Morel et al.13 also found significant differences in these indices between whites and Africans. Haseltine et al.8 report significant differences in CH values between 3 racial groups. Although these differences were due to variations in biometric factors, one of the most important factors in these differences was refractive error. Highly myopic populations have been shown to have lower CRF and CH values; therefore, East Asian populations are expected to have lower mean values. Central corneal thickness can also affect variations in corneal biomechanical indices; most East Asian populations have thinner corneas than European and Iranian populations.21

In our study, girls had a higher CRF than boys; this was true even after adjusting for CCT. However, we did not find a statistically significant difference in CH between boys and girls. Narayanaswamy et al.11 found significantly higher CRF and CH readings in women in their study of elderly Chinese people. Fontes et al.22 studied healthy Brazilian patients and found significantly higher values of both corneal biomechanical indices in girls. In a study of 3 races, Haseltine et al.8 observed higher CH values in women. Biometric indices, especially AL, play a role in the difference between sexes. From previous studies,23,24 we know that girls have a smaller AL than boys. Also, findings in some studies9,25 suggest an inverse association between biomechanical properties and AL. Thus, the higher CRF and CH values in girls may be due to their smaller AL.

An interesting finding was the difference between CH and the CRF; the difference between CH and the CRF was relatively small in our study, especially in boys, similar to findings in eyes with keratoconus. Because our study population was of normal individuals, additional studies should be performed, especially in patients versus in a normal population.

In our study, age had no significant correlation with the CRF or CH. Results in other studies are inconclusive in this regard. Chang et al.26 studied a sample of subjects similar to our students in age; in agreement with our findings, they found no significant change in the CRF or CH with age. Similarly, Lim et al.10 observed no significant change in these indices with age in their sample of 12- to 15-year-olds. Narayanaswamy et al.11 found a significant decrease in CRF and CH values with age in a sample of 44- to 83-year-old Chinese people.

In a study of corneal biomechanical properties, Kamiya et al.16 examined age-related changes in 19- to 89-year-old people and observed that CRF and CH values significantly decreased with age without any change in CCT. In a 19- to 48-year-old sample, Plakitsi et al.20 found that only CH significantly decreased with age. Leite et al.19 also showed a significant decrease in CH with age in 24- to 90-year-olds. Overall, results indicate that corneal biomechanical properties change less before the age of 20 years and a decrease has been observed mostly in studies with older samples. In other words, the energy-absorption capability of the cornea appears to be stable in the first 20 years of life and starts to decrease thereafter.

In a study by Daxer et al.,27 there was an age-related increase in stromal fibrils. This was attributed to an increase in collagen molecules with aging. Also, aging is associated with increased crosslinking between fibrils that, along with increased glycation due to crosslinking between fibrils, leads to increased corneal rigidity. These changes are contradictory to the age-related decrease in the CRF and CH. As mentioned, some studies observed a decrease in CH only, while the CRF, which is related to corneal rigidity, showed no change with age. Nonetheless, the increased IOP and decreased CCT associated with age may explain the age-related decrease in corneal biomechanical properties. It is important to consider that the corneal resistance and energy-absorption capability of the cornea decline when assessing patients seeking laser refractive surgery, especially middle-aged and elder patients. Preoperative measurements should be taken to ensure they are at an acceptable level.

In our study, corneal biomechanical properties directly correlated with CCT and mean K values. Central corneal thickness is one of the most important factors shown to correlate with corneal biomechanical properties in several studies. In addition to clinical studies, the correlation between CCT and corneal biomechanical properties has been found in several population-based studies. For example, increased biomechanical properties with increasing CCT was reported by Narayanaswamy et al.11 in elderly Chinese people, by Lim et al.10 in Singapore children, by Jiang et al.12 in 11- to 65-year-old Chinese people, and by Chang et al.26 in 7- to 18-year-olds. Also, in most of these studies (Leite et al.19), the CRF had a stronger association with CCT, and this was confirmed in our study. The direct correlation between CH and CRF values and CCT was expected.

Our multiple linear regression model showed that a long AL was significantly correlated with a decrease in CH. This correlation was also reported by Song et al.,25 Huang et al.,9 Narayanaswamy et al.,11 and Chang et al.26 The mechanism of the decrease in CH in eyes with a long AL is not clear; however, it seems as though the sclera changes and the direction of the collagen fibrils in myopia result in the decrease in CH. Deformity of the sclera in individuals prone to myopia has a greater effect on this decrease than the secondary changes of the increase in AL.

What Was Known

  • The relationship between corneal biomechanical properties and diseases such as keratoconus, Fuchs corneal dystrophy, and glaucoma has brought these indices to the attention of ophthalmic researchers.

What This Paper Adds

  • This study describes the normal distribution of CRF and CH properties in 6- to 18-year-old Iranian students. In the study, the p1 area decreased with age.

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