The variation in axial length in office hours causes a diopter change in the intraocular lens power calculation

Abstract

Purpose

To investigate whether diurnal changes in biometric parameters at different times of the day are visible and to analyze whether the variations could have clinical significance in the process of intraocular lens (IOL) power calculation.

Methods

Phakic eyes measured by IOLMaster 700 above the age of 16 were included, with the exclusion of previous surgery. Measurements were taken between 7:00 and 15:00 and data were treated in hourly groups within this range. Data such as age, sex and biometric parameters (axial length (AL), anterior chamber depth, central corneal thickness, white-to-white distance, keratometry readings, lens thickness) were used besides the hour:minute time of the examination.

Results

Biometric data from 32,596 eyes were used (38.89% males). There were no statistically significant differences in age and biometric parameters between the office-hour groups (p > 0.05), excluding the AL. The AL at the end of the day was 0.198 mm longer for male and 0.197 mm longer for female compared to the beginning of the office day. Accordingly, the results of IOL power calculation varied between 21.0 and 20.0 D for male, and 21.5 D and 20.5 D for the female population.

Conclusion

The results suggest that the assessment of AL may be affected by the intraday time of the biometry. This variation is clinically significant and may have implications for the evaluation of AL.

Keywords

Axial length biometry diurnal changes intraocular lens power calculation

Introduction

The measurable parameters of the human eye are not static throughout our lives. Biometric parameters change as we grow from childhood, and changes in refractive status also well described. Additionally, several parameters undergo age-related gradual changes in adulthood, such as the meridian of keratometric values,^1,2 anterior chamber depth,³ crystalline lens thickness,⁴ and corneal white-to-white distances.^5–7 In addition to slow, age-related changes, seasonal changes in axial length (AL) have also been observed in young adults and have been linked to changes in melatonin secretion.⁸

Besides, it has shown for more than 30 years that some measurable parameters of the eye undergo diurnal changes. Such changes have been described for intraocular pressure (IOP),^9–13 central corneal thickness (CCT),^13–15 topography,^16,17 keratometry reading,^18,19 higher order aberration (HOA)^20,21 and AL,^9,22,23 but it is known that anterior chamber depth (ACD),¹⁶ retinal nerve fiber layer (RNFL), retinal and chorioideal thickness²⁴ and some tear parameters^25,26 can also change. The diurnal variation in the measurable parameters of the eye was also significant in children, which the author suggests may have important implications for the development of myopia in children.²⁷ In this study, axial length and IOP varied approximately in phase with each other and in antiphase with choroidal thickness.²⁷

Diurnal changes in the parameters of the eye may provide insight into physiological changes and have clinical implications. It is important to take into account the higher values of diurnal changes in IOP in the morning when assessing IOP. It is unclear whether other parameters, even if they vary during the day, reach clinically significant levels that affect the accuracy of intraocular lens (IOL) power calculations. The objective of our study was to investigate whether diurnal changes in biometric parameters measured by an optical biometer at different times of the day are visible, using a large cross-sectional database. Additionally, we aimed to analyze whether the observed changes could have clinical significance in the process of IOL power calculation. This would help determine whether we should take into account the time of measurement to increase accuracy.

Methods

The study protocol complied with the principles of the Declaration of Helsinki, revised in 2013, and was approved by the Regional/Institutional Scientific and Research Ethics Committee of the Central Hospital and University Teaching Hospital of Borsod-Abaúj-Zemplén County, Miskolc, Hungary with the identification number BORS-03/2024. Due to the retrospective nature of the study, the requirement to obtain written informed consent was waived.

All phakic eye measurements at office time in the database above the age of 16 years were indiscriminately included in the retrospective data collecting, the only exclusion being previous laser vision correction. We therefore used a database measured according to our daily routine, taking biometric data on the same individual only once a day. One measurement was taken for each patient, predominantly without cycloplegia.

For the measurements, the same Zeiss IOLMaster 700 (software version 1.50.7.40411) was used. Measurements were taken between 09 July 2016 and 14 November 2023. The office hours were defined in the GMT + 1.0 time zone between 7:00 and 15:00 h and the data were treated in hourly groups within this range. The exact time setting was correct throughout the examination. The median time for biometric measurements was 10:44:12.

For data collection, anonymized patient data such as age, biological sex and biometric parameters (axial length, anterior chamber depth, central corneal thickness, corneal white-to-white distance, keratometry readings, lens thickness), obtained from IOLMaster 700, were used. The biometric values in this exported csv file include the exact hour:minute time of the examination. The measurement data for the whole population were thus sorted by the hour:minute data and groups were created according to the test hour intervals. Data from these groups, i.e., eyes measured in one-hour intervals, were used for further analysis.

Descriptive statistics were performed to determine mean, median, standard deviation (SD) and range. The distribution of the data was estimated using the Shapiro-Wilk test and normality was excluded for all variables included (p < 0.001), so we used the Mann-Whitney test to compare groups of data, the Kruskal-Wallis test to compare three or more non-matched groups and Spearman correlation test to quantify the relationship between two variables.

For data management and statistical data processing, we used Microsoft Excel 2021 and MedCalc Statistical Software version 13.0.6 (MedCalc Software BvBA, Ostend, Belgium). A P-value below 0.05 was considered significant.

Results

Biometric data from 32,596 eyes were used (38.89% males, 61.11% females). Age and descriptive statistics of the biometric parameters are presented in Table 1. For all parameters in Table 1, p was <0.05 between the female and male groups, except in the case of LT.

Table 1.

The means, the SDs (standard deviation) and the ranges of age and biometric parameters of the examined eyes.

		Overall	Female	Male
age (year)	Mean	69.71	70.43	68.57
	Median	71.55	72.38	70.19
	SD	12.79	12.85	12.61
	Range	16.0–98.28	16.0–98.28	16.0–98.02
AL (mm)	Mean	23.46	23.29	23.73
	Median	23.25	23.05	23.57
	SD	1.46	1.47	1.39
	Range	15.06–32.43	15.06–31.35	15.18–32.43
R1 (mm)	Mean	7.76	7.71	7.84
	Median	7.75	7.70	7.83
	SD	0.29	0.27	0.29
	Range	6.05–10.72	6.05–10.72	6.35–9.94
R2 (mm)	Mean	7.60	7.55	7.67
	Median	7.59	7.55	7.67
	SD	0.28	0.27	0.29
	Range	5.27–10.09	5.46–10.09	5.27–9.41
ACD (mm)	Mean	3.08	3.02	3.16
	Median	3.06	3.00	3.15
	SD	0.43	0.42	0.44
	Range	1.16–7.15	1.16–7.15	1.20–6.43
LT (mm)	Mean	4.55	4.55	4.54
	Median	4.59	4.60	4.57
	SD	0.59	0.57	0.63
	Range	2.05–7.34	2.06–7.34	2.05–7.12
CCT (µm)	Mean	547.81	544.75	550.11
	Median	545.196	543.31	549.12
	SD	36.31	35.63	37.15
	Range	377.55–987.12	377.55–790.13	421.71–987.12
WTW (mm)	Mean	11.84	11.76	11.95
	Median	11.83	11.76	11.95
	SD	0.42	0.40	0.42
	Range	9.22–15.70	9.22–15.24	9.53–15.70

AL: axial length, R1 and R2: corneal radius of curvature in the flattest and steepest meridian, ACD: anterior chamber depth, LT: lens thickness, CCT: central corneal thickness, WTW: corneal white-to-white distance.

There were no statistically significant differences in mean age between the different office-hour groups (Kruskal-Wallis p > 0.05), nor were ACD, LT, CCT, and WTW statistically different between the different groups (Kruskal-Wallis p > 0.05). The largest average age difference between the subgroups of office hours in the male group was 2.28 years and 1.46 years for women.

Age and AL were significantly correlated in both the male and female populations (r = −0.12; p < 0.001 and −0.147; p < 0.001, respectively), and this correlation was also observed when the office-hours groups were separated (all groups r value was between −0.11 and −0.17, with a significance level of p < 0.001). The AL difference between the end (15:00 h) and the beginning (7:00 h) of the office day was 0.223 mm for the total population, 0.198 mm for the male group and 0.197 mm for the female group.

The IOL power calculation was performed based on the change in the diurnal variation of the AL, using the Barrett Universal II formula (calc.apacrs.org/barrett_universal2105). In all three tables (Tables 2–4), the biometric values corresponding to the respective data group (overall, male, female) were used for IOL power calculation, including the optional LT and WTW values as well. When using an A-constant of 118.9, only the difference in axial lengths during office hours shows a difference in IOL diopter of up to 1.0 D. This is calculated for the most likely residual refractive error value commonly used, as shown in tables. If the database is split by gender, the data in Tables 3 and 4 is obtained for the IOL power calculation. Calculated using the AL value for the male population, the IOL diopter value for conventional calculation varies between 21.0 and 20.0 D, for the female population these values are between 21.5 D and 20.5 D.

Table 2.

IOL power calculation results in the whole examined population (regardless of biological sex) as a function of office hours.

Office hours	Mean AL (mm)	Most probable IOL D	Predicted residual sphere (D)
7.00–8.00	23.394	21.5	−0.19
8.00–9.00	23.406	21.5	−0.22
9.00–10.00	23.416	21.5	−0.24
10.00–11.00	23.447	21.0	+0.04
11.00–12.00	23.525	21.0	−0.14
12.00–13.00	23.506	21.0	−0.10
13.00–14.00	23.523	21.0	−0.14
14.00–15.00	23.617	20.5	−0.01

The postoperative refraction is set to the nearest practical negative value to zero that is commonly used.

Table 3.

IOL power calculation results in the male population as a function of office hours.

Office hours	Mean AL (mm)	Most probable IOL D	Predicted residual sphere (D)
7.00–8.00	23.681	21.0	−0.15
8.00–9.00	23.729	21.0/20.5	−0.26/+0.1
9.00–10.00	23.674	21.0	−0.13
10.00–11.00	23.721	21.0/20.5	−0.24/+0.12
11.00–12.00	23.814	20.5	−0.1
12.00–13.00	23.755	20.5	+0.04
13.00–14.00	23.863	20.5/20.0	−0.22/+0.14
14.00–15.00	23.879	20.5/20.0	−0.26/+0.1

The postoperative refraction is set to the nearest practical value to zero that is commonly used. Sometimes, according to the operator's preference, there are two choices for the refractive output, both are indicated here.

Table 4.

IOL power calculation results in the female population as a function of office hours.

Office hours	Mean AL (mm)	Most probable IOL diopter	Predicted residual sphere (D)
7.00–8.00	23.232	21.5	−0.08
8.00–9.00	23.190	21.5	+0.02
9.00–10.00	23.258	21.5	−0.15
10.00–11.00	23.281	21.5/21.0	−0.2/+0.15
11.00–12.00	23.325	21	+0.05
12.00–13.00	23.332	21	+0.03
13.00–14.00	23.312	21	+0.08
14.00–15.00	23.429	21.0/20.5	−0.2/+0.15

Discussion

The eye's biometric parameters undergo age-related, seasonal and diurnal changes. Circadian rhythms are natural fluctuations of physiological parameters that follow an approximately 24-h cycle. When circadian rhythms are synchronous with the 24-h diurnal cycle, they are considered diurnal rhythms. Diurnal variations of ophthalmic parameters are known,^9,10–24 although there is evidence that some parameters (IOP, RNFL and central macular thickness) do not change during the day.²⁸ The causes of diurnal variation may be diverse.

Some parameters, such as CCT, may be altered due to reduced corneal oxygenation, which may cause hypoxia-induced swelling under the closed eyelid, but slight fluctuations in CCT during the day^14,15 have also been explained by hormonal factors or gender differences.^29,30 Differences in diurnal variation in corneal curvature between men and women have also been described, which may be explained by hormonal factors. Clinically significant K-changes within a day were observed in women but not in men.¹⁹

In the present study, we have also analyzed male/female differences and, using a large database, we describe that AL values measured with a swept-source optical biometer, at least according to the processing of cross-sectional data, differ clinically significantly between different times of day.

However, apart from the variation in AL, no statistical difference was found for the other measured values (K, ACD, LT, CCT, WTW). Thus, in our cross-sectional database, parameters other than AL did not show such diurnal variation, at least during the daytime hours of the study; i.e., we cannot exclude that this variation is present in our own database, but only outside the study time-period.

The diurnal variation of AL was first described in animal models,^31,32 and later relatively few and explicit small case studies of diurnal variation in axial length were published.^9,22,23,33 About 20 years ago, Stone et al. reported on diurnal fluctuations in axial length using an unnamed tool using partial coherence interferometry (PCI).²² Shortly afterwards, Wilson et al., in a study of ten young adults, demonstrated that both IOP and PCI-measured AL exhibited diurnal variation, but as they concluded, “diurnal IOP fluctuations do not appear to cause diurnal axial length fluctuations.”.²³ Then, in a small sample size study, Read et al. demonstrated that axial length measured by IOLMaster and IOP measurements taken at six different times of the day exhibited fluctuations, with an average fluctuation of AL of 0.046 mm. The authors noted that the association between AL and IOP variation was not strong.⁹

No significant differences in age composition or sex ratio were observed in our database as the office hours progressed. Therefore, the hypothesis that the average age or sex composition of the population at different times of the day might be different, which could explain the described change, was also rejected.

The diurnal variation in axial length for the predominantly young eyes analyzed above averaged between 22 and 45 μm, with smaller AL values typically observed during the night.^{22,23,25,27,33–37} Our own data suggests that significant variations in axial length at different times of the day could also result in significant (≥0.5 D) variations in IOL power calculation, which should be reflected in the postoperative prediction error.

An average AL difference of 0.223 mm was found over time in this extensive database measured by a swept source OCT-based device. According to the Barrett Universal II formula, this difference in axial length results in a variation of 0.5–1.0 D in the IOL diopter, considering the most likely planned residual refractive error. To ensure accurate results, we calculated the IOL diopter planned in the direction of the small myopic residual sphere likely to be chosen by the vast majority of surgeons. This was done because IOL diopters produced in 0.5 D increments cannot always follow the change in axial length described on a continuous scale and the need for a predicted residual refractive value. Additionally, we considered some IOLs with a smaller residual sphere despite minimal hyperopic postoperative refractive error. Possible diurnal variations in other parameters, mainly keratometry and ACD, could offset the effect of AL changes. However, in our dataset, the other parameters did not diverge at different examined times of the day.

The IOLMaster 700 has repeatability and reproducibility values of 0.014 and 0.023 mm for AL³⁸ and a measurement standard deviation of 0.005 mm according to the Zeiss manual.³⁹ Despite the fact that several authors^22,23 point out that the diurnal changes described are well above the corresponding values of the measurement tools, Stone et al. describe these changes as too small to be detectable subjectively as shifting image clarity.²²

Also, predominantly cross-sectional studies have demonstrated a decrease in AL with age, which is not caused by myopic progression. A review analyzing these articles also reveals potential flaws in cross-sectional studies.⁴⁰ The observed age-related decrease in AL is also interesting because refractive surgery (refractive surgeries, refractive lens exchange) is assumed to be unaffected by changes in axial length in adulthood.⁴⁰ longitudinal studies with 5–10 years follow-up reach a similar conclusion, i.e., a decrease in AL is also confirmed in the relatively short term.^41–43

This line of thinking is comparable to that used in cross-sectional studies that describe the changes in astigmatism with age.^1,2 In these studies, longitudinal changes are inferred from the results of cross-sectional studies, although there are real longitudinal studies on the subject, no doubt with relatively short follow-up.⁴⁴ It is important to note that the description of the age-varying parameters and the change within a day are different in terms of feasibility and comparisons are speculative.

It is unclear whether the clinically significant variance described is solely due to the diurnal cycle, as no other explanation can be found for the observation. This raises the question of whether there is a methodological, device-related or population-level flaw that causes the clinically significant difference analyzed in our study. We also analyzed the age and sex distribution of the population and found no difference at the beginning and end of the office hours. The described difference in AL is of a magnitude that cannot be explained by the diurnal change in AL described earlier in the literature alone. Therefore, we hypothesized that the change in AL, which is an order of magnitude larger than previously described, is not only due to a physiological diurnal component (including speculative decrease in sclera-elasticity and increased dehydration during the day), but also to some hitherto unknown methodological or instrument-related component. To confirm that the results are not biometer-dependent, it would be beneficial to analyze the results of a large number of biometric data obtained with other devices using a similar methodology.

If this large deviation of AL from the examination hour is indeed based on a diurnal cycle, it would be interesting to analyze the postoperative refractive outcome as a function of the time of day of the preoperative biometric measurements, examining which time of day had the smallest prediction error.

Undoubtedly, we have used cross-sectional data in our study to suggest that diurnal variation exists within individuals. Since we worked with a very large and in many respects heterogeneous case population, we believe that at least some of the changes described in AL are due to the diurnal cycle. Assuming this, in light of the results, it seems that we should potentially take into account the time of day when performing the biometry when calculating the IOL power, but to do so in practice and standardize this in our own daily routine would be both difficult and highly unusual.

The limitation of our study, besides the retrospective method, is the high heterogeneity of the patient data, but the unfiltered data, in our opinion, show a much real-word situation. The other limitation is the cross-sectional nature of the study, which we have analyzed as a drawback, but a longitudinal study on such a large population does not seem feasible. However, apart from these, this is probably the largest sample-sized study of diurnal variation in biometric parameters using a single, state-of-the-art, swept-source optical biometer.

In summary, our results suggest that the assessment of AL may be affected by the intraday time of the biometry. This variation is clinically significant and may have implications for the evaluation of AL. As the variation is clinically significant, it is not reassuring to practicing ophthalmologists that we should evaluate the AL and therefore the diopter of the implanted IOL in this light, which is certainly not standard practice today. Obviously, direct measurement of possible longitudinal changes would be necessary on a large number of cases to draw final conclusions.

What was known

Measurable ophthalmic parameters may vary with age, season and time of day.

Gender differences in ophthalmic parameters are also known and gender-dependent variations in some parameters have been observed.

Axial length is one of the most influential parameters in the calculation of IOL power.

What this paper adds

We described large, clinically significant diurnal axial length variations in a cross-sectional database, measured with a swept-source biometer.

A methodological and/or device-dependent factor is also likely to be behind the variation in axial length, which is much larger than the diurnal change described earlier.

Synopsis

The axial length can be affected by the time of day of the biometry, which can have a clinically significant effect on the outcome of the intraocular lens power calculation.

Footnotes

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

ORCID iDs

Gabor Nemeth

Agnes Revak

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