The Effect of Age on Increasing Susceptibility to Retinal Nerve Fiber Layer Loss in Glaucoma

Abstract

Purpose: To determine whether aging modifies the effect of intraocular pressure (IOP) on progressive glaucomatous retinal nerve fiber layer (RNFL) thinning over time.

Methods: This was a retrospective cohort study involving patients with glaucoma or suspected of having glaucoma who were followed over time from the Duke Glaucoma Registry. Rates of RNFL loss from spectral-domain optical coherence tomography (SD-OCT) were used to assess disease progression. Generalized estimating equations with robust sandwich variance estimators were used to investigate the effects of the interaction of age at baseline and mean IOP on rates of RNFL loss over time. Models were adjusted for gender, race, diagnosis, central corneal thickness, follow-up time, and baseline disease severity.

Results: The study included 85,475 IOP measurements and 60,026 SD-OCT tests of 14,739 eyes of 7814 patients. Eyes had a mean follow-up time of 3.5 ± 1.9 years. The average rate of change in RNFL thickness was -0.70 µm/year (95% confidence interval, -0.72 to -0.67). There was a significant interaction between age and mean IOP and the rate of RNFL loss (P = 0.001), with older eyes having significantly faster rates of RNFL loss than younger ones for the same level of IOP. The effect of IOP on rates of change was greater in the inferior and superior regions of the optic disc.

Conclusions: Age is a significant modifier of the relationship between IOP and glaucomatous loss in RNFL thickness over time. Older patients may be more susceptible to glaucomatous progression than younger patients at the same level of IOP.

Figure 1.

Trajectories of changes in RNFL thickness over time across levels of IOP for 40-, 60-, and 80-year-old average subjects from the whole sample. Other covariates were set to their mean values. Capped spikes indicate 95% CIs.

Figure 2.

Contour plot showing the effect of the interaction between mean IOP and age on rates of RNFL thickness change over time. Readers can examine the x-axis values to estimate the influence of average IOP (y-axis) on the rates of RNFL thickness change over different age groups. The average rate of RNFL thickness loss (–0.70 µm/year) was subtracted from the predicted rate of change for each given age and mean IOP, so the results can be interpreted as either protective (green, or slower rates of change) or harmful (warmer colors, or faster rates of change) in relation to the average rate of change of the sample.

Figure 3.

Effect of the interaction term (baseline age and average IOP during follow-up) on the rates of peripapillary RNFL thickness change for each sector. Coefficients were derived from multivariable models adjusted for gender, race, glaucoma diagnosis, CCT, follow-up time, and baseline RNFL thickness in each sector. Asterisk indicates statistical significance (P < 0.05). Sectors start at the temporal cardinal point as 0° (clock hour 9), proceeding clockwise around the optic disc in 30° steps, correlating to the report of the Spectralis SD-OCT. INF, inferior; NAS, nasal; SUP, superior; TMP, temporal.

Figure 4.

Polar plots illustrating the estimated rates of change in RNFL thickness according to the sectors around the optic disc for subjects 40 and 80 years of age and different levels of average IOP during follow-up. It can be seen that the impact of IOP was significantly greater in older eyes compared to younger ones and that the effect was markedly greater in the inferior and superior sectors of the optic nerve, in terms of both absolute loss (µm/year) (A) and percentage of loss from the baseline thickness (%/year) (B) for each sector.