1. Greater fluctuation in intraocular pressure (IOP) over several years is significantly and independently associated with oretinal nerve fibre layer (RNFL) thinning, an indicator of open-angle glaucoma disease progression.

Evidence Rating Level: 2 (Good)

Study Rundown: In patients with open-angle glaucoma, intraocular pressure (IOP) is the sole modifiable risk factor for disease progression. However, glaucoma has been found to progress in the context of a wide range of IOP values, and so it has been proposed that IOP variability could have a stronger influence on disease course than IOP magnitude alone. Previous studies yielded inconclusive results when evaluating the association between long-term IOP variability and visual field progression. Therefore, this current retrospective study examined the association between long-term IOP variability and rate of retinal nerve fibre layer (RNFL) thinning, a proxy for glaucoma disease progression. The study population was taken from 2 pre-existing glaucoma studies, with patients being included if they had at least 2 years of follow-up and 4 visits, to measure IOP and RNFL thinning. As such, this study was limited to evaluating long-term variability over months to years, as opposed to circadian or short-term variability. Overall, the study found that RNFL thinning was associated with greater long-term IOP variability and IOP range, even after adjusting for mean IOP.

Click here to read the study in JAMA Ophthalmology

Relevant Reading: Normal tension glaucoma—a practical approach

In-Depth [retrospective cohort]: The study population consisted of patients with perimetric and preperimetric glaucoma, with follow-up visits between 2008 and 2020. IOP was measured using calibrated tonometer, and RNFL thinning was measured wit optical coherence tomography (OCT). Mean IOP was the average of all IOP measurements in follow-up, whereas IOP fluctuation was defined as the standard deviation of these measurements. In total, there were 508 patients included (55.1% female, 55.3% white), with a mean (SD) age of 65.5 (11.0 years). There were 815 eyes represented in the study, 564 with perimetric glaucoma and 251 with preperimetric. There was a mean of 10.5 IOP measurements and 10.2 OCT images, acquired over an average 6.3 years (95% CI 6.2-6.5) of follow-up. The mean IOP fluctuation was 2.4 mm Hg (95% CI 2.3-2.5), the mean IOP range was 7.4 mm Hg (95% CI 7.1-7.7), and the mean IOP was 14.8 mm Hg (95% CI 14.5-15.0). After adjusting for mean IOP and other covariates, there was a significant association between RTFL thinning and greater IOP fluctuation, at -0.22 um per 1-mm Hg increase (95% CI -0.26 to -0.15, p < 0.001). As well, there was a significant association between RTFL thinning and increased IOP range, at -0.05 um per 1-mm Hg increase (95% CI -0.06 to -0.03, p < 0.001). Finally, there was also an association between RTFL thinning and higher mean IOP, at -0.03 um per 1-mm Hg increase (95% CI -0.05 to -0.01, p = 0.005). Overall, this study demonstrated that increased long-term IOP fluctuation is an independent predictor for progression of open-angle glaucoma, not solely the IOP magnitude.

Image: PD

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