Head-down Posture in Glaucoma Suspects Induces Changes in IOP, Systemic Pressure, and PERG That Predict Future Loss of Optic Nerve Tissue

Abstract

Purpose: To obtain pilot data on posture-induced changes of intraocular pressure (IOP), systemic pressure, and pattern electroretinogram (PERG) predictive of future optic nerve tissue loss glaucoma suspects (GSs).

Methods: Mean peripapillary retinal fiber layer thickness (RNFLT) was measured with optical coherence tomography 2 times/year in 28 GS aged 58±8.9 years over 5.0±0.73 years. All patients had a baseline PERG, IOP, and brachial blood pressure measurements in the seated and -10 degrees head-down-body-tilt (HDT) position. Outcome measures were seated/HDT PERG amplitude and phase, IOP, mean arterial blood pressure, and estimated ocular perfusion pressure. An additional group of 11 similarly aged controls aged 56.9±13 years was tested for comparison.

Results: Although all GS had initial RNFLT in the normal range, 9/28 of them developed significant (P<0.05) loss of mean RNFLT [thinners (T)] over the follow-up period as opposed to 19/28 who did not [nonthinners (NT)]. Significant (P<0.05) differences between similarly aged controls, NT, and T were found in PERG amplitude, PERG phase, mean arterial blood pressure, IOP, and ocular perfusion pressure. A nominal logistic regression using baseline PERG and hemodynamic variables was able to distinguish T from NT with an area under receiving operator characteristic of 0.89 (SE, 0.07).

Conclusions: Baseline PERG, IOP, and systemic blood pressure, together with their changes upon HDT, may have predictive value for future loss of optic nerve tissue in GS. This study supports the rationale for a full-scale clinical trial to identify patients at high risk of development of glaucoma.

Figure 1

Changes of mean RNFL thicknesses over ~ 5 years in randomly selected eyes of 28 glaucoma suspects. Initial and final RNFL thicknesses were the average of first 3 and last measurements of the longitudinal series, respectively. Note that 9/28 eyes had losses of RNFL thickness larger than 5.4 μm, which represents the ± 95% confidence interval of the normal intervisit test-retest variability of mean RNFL thickness according to Budenz et al, 2008. In both thinners and the non-thinners, the initial mean RNFL thickness was in the normal range according to Budenz et al., 2007. In both thinners and the non-thinners, there was no significant correlation between initial RNFL thickness and change of RNFL thickness (Non thinners, R²=0.026; thinners, R²=0.014). Thirteen patients (red symbols) received IOP-lowering drops during the follow-up period.

Figure 2

Pattern electroretinogram amplitude (A) and phase (B) recorded in the seated (blue bars) and head-down (red bars) position from randomly selected eyes of Similarly-Aged Controls (SAC, n=11), RNFL non-thinners (NT, n=19), and RNFL thinners (T, n=9). Bars represent the mean and the SEM. Note that the PERG amplitude and phase tend to be smaller in RNFL thinners compared to RNFL non-thinners and similarly-aged controls. Also note that the PERG amplitude decreases upon HDT in non-thinners and thinners but not in controls.

Figure 3

A: Intraocular pressure (IOP), B: mean arterial pressure (MAP) and C: ocular perfusion pressure (OPP) measured in the seated (blue bars) and head-down (red bars) position in randomly selected eyes of similarly-aged controls (SAC, n=11), RNFL non-thinners (NT, n=19), and RNFL thinners (T, n=9). Bars represent the mean and the SEM. Note in A that IOP increases in all groups upon HDT. Also note in B and C that MAP and OPP tend to be higher in the thinners group compared to non-thinners and similarly-aged controls. Note in C that OPP tends to increase upon HDT in non-thinners and thinners but not in controls.

Figure 4

Relationship between posture-dependent PERG amplitude and phase coefficients (PERG component) and Mean Arterial Pressure upon head-down posture (MAP on tilt) in randomly selected eyes of a population of 28 glaucoma suspects who were followed at least 4 years with OCT. Larger, filled symbols represent eyes that developed mean RNFL thinning larger than 5.4 μm (grey, P<0.05; black, P<0.01). Small open symbols represent eyes without significant RNFL thinning. Coefficients were obtained by backward logistic regression. Note the relatively good separation between RNFL thinners and non-thinners.