Time-of-Year Variation in Intraocular Pressure

Abstract

Précis: In this study conducted in Chicago, IL, intraocular pressure (IOP) level was found to have a subtle, but measurable, annual pattern. Reasonable evidence is presented for a time-of-year variation in IOP. Adequate numbers of subjects must be studied to detect this small variation.

Purpose: The aim was to investigate the relationship between IOP and time of year.

Methods: During a separate investigation, patients from 2011 to 2018 (dataset A, N=3041) in an urban, academic facility in Chicago, IL received an examination that included Goldmann applanation tonometry. Regression analyses assessed the relationship between time of year and IOP. Two additional datasets, 1 collected in a similar manner during 1999 and 2002 (dataset B, N=3261) and another consisting of all first visits during 2012 and 2017 (dataset C, N=69,858), were used to confirm and further investigate trends.

Results: For dataset A, peak mean IOP occurred in December/January (15.7±3.7/15.7±3.8 mm Hg) and lowest in September (14.5±3.1 mm Hg). The analysis suggested conventional quarterly analysis (January to March, etc.) can conceal time-of-year relationships because of inadequate statistical power and timing of IOP variation. Multiple linear regression analysis, with a November-to-October reordering, detected an annual, downward IOP trend (P<0.0001). Analysis of dataset B confirmed this trend (P<0.001). Fourier analysis on datasets A and B combined supported a 12-month IOP cycle for right/left eyes (P=0.01/P=0.005) and dataset C provided stronger evidence for an annual periodicity (P<0.0001). Harmonics analysis of dataset C showed a repeating pattern where IOP trended downward around April, and then back upward around October.

Conclusions: This analysis strongly supports a demonstrable annual, cyclical IOP pattern with a trough to peak variation of ≈1 mm Hg, which has a seasonal relationship.

Fig 1.

Flow diagram summarizing subject participation and inclusion for the primary dataset (Dataset A).

Fig 2.

Plots using the primary dataset A. (Upper left): Monthly mean plots using a November-to-October ordering, showing a downward IOP trend. (Lower left): Least squares regression line and 95% confidence interval lines calculated using the individual data points rather than monthly means. (Right): Periodogram to test for cyclical IOP patterns, truncating time period from January 2012 to December 2017. A peak is present near the 0.08 frequency, which would be expected with a yearly cycle (6 years, cycles / 72 months = 0.083). Although the dominant peak suggests a 12-month IOP cycle, statistical significance is not reached with this dataset (Fisher’s g-statistic, P=0.21).

Fig 3.

Plots using the older dataset B. (Upper left): Monthly mean plots using a November-to-October ordering, showing a downward IOP trend. (Lower left): Least squares regression line and 95% confidence interval lines calculated using the individual data points rather than monthly means. (Right): Periodogram to test for cyclical IOP patterns, truncating time period from January 2000 to December 2001. A peak is present near the 0.08 frequency, which would be expected with a yearly cycle (6 years, cycles / 72 months = 0.083). Although the dominant peak suggests a 12-month IOP cycle, statistical significance is not reached with this dataset (Fisher’s g-statistic, P=0.27).

Fig 4.

Plots using datasets A and B combined. (Top): Scatterplots of right and left eye monthly means using truncated data from dataset B (January 2000 thru December 2001) and dataset A (January 2012 thru December 2017). (Bottom): Corresponding periodograms. Yearly cycles are suggested for both eyes with statistically significant peaks present near the 0.08 frequencies (arrows, P=0.01/0.005).

Fig 5.

Plots using the dataset C consisting of institutional patient first-visits. (Left): Least squares regression line and 95% confidence interval lines calculated using the individual data points rather than monthly means. A downward IOP trend is observed, consistent with datasets A and B. (Upper right): Monthly means scatterplot for the 72-month time period. (Lower right): Corresponding periodogram shows a dominant peak near a frequency of 0.08 with strong statistical significance (P<0.0001).

Fig 6.

Harmonics analysis using monthly mean IOP values of right eye, first-visit Goldmann IOP from patients seen at institution from January 2012 thru December 2017 (dataset C). The 12-month data from each year was expanded into a Fourier series showing approximations after keeping the first order (1 cycle/year) and second order harmonics.