Intraocular Pressure Variability Associated with Structural Changes in Glaucoma

Robert N. Weinreb, MD

New findings indicate intraocular pressure (IOP) variability was independently associated with retinal nerve fiber layer (RNFL) thickness changes in a study cohort of patients with glaucoma, even after adjustment for mean IOP in follow-up.

Both IOP fluctuation and IOP range were more strongly associated with RNFL thinning compared with mean IOP in the cohort.

“This finding is significant, as the current mainstay of glaucoma care is lowering IOP to prevent glaucomatous progression,” wrote study author Robert N. Weinreb, MD, Hamilton Glaucoma Center, Shiley Eye Institute, Viterbi Family Department of Ophthalmology, University of California, San Diego. “Our study suggests that in addition to monitoring IOP magnitude, clinicians should consider IOP variability in the evaluation of patients with glaucoma.”

Prior research suggests higher IOP variability may be a risk factor for glaucomatous progression potentially more than IOP magnitude, but there have been discrepancies in the definition of IOP variability. Weinreb and colleagues evaluated the association between long-term IOP variability and optical coherence tomography (OCT)-based rate of RNFL thinning.

The retrospective longitudinal cohort study included patients with preperimetric and perimetric glaucoma enrolled from the Diagnostic Innovations in Glaucoma Study (DIGS) and African Descent and Glaucoma Evaluation Study (ADAGES). Those with at least 4 visits and 2 years of follow-up for OCT and IOP measurement in the corresponding time period from December 2008 to October 2020.

A total of 815 eyes (564 with perimetric glaucoma and 251 with preperimetric glaucoma) from 508 patients with imaging follow-up were studied for a mean of 6.3 years from December 2008 to October 2020.

Demographic data of the 508 included patients show 280 (55.1%) were female, 195 (38.4%) were African American, 24 (4.7%) were Asian, 281 (55.3%) were White, and 8 (1.6%) were another race or ethnicity. The reported mean age was 65.5 years.

Based on a table describing the clinical characteristics of participants by OCT progressor group, the mean rate of retinal nerve fiber layer changes was -0.67 (95% CI, -0.73 to -0.60) μm per year.

In multivariable models, a faster annual rate of RNFL thinning was associated with a higher mean IOP (-0.03 [95% CI, -0.05 to -0.01] μm per 1-mm Hg higher; P = .005) and IOP fluctuation (-0.20 [95% CI, -0.26 to -0.15] μm per 1-mm Hg higher; P <.001).

Moreover, a faster annual rate of RNFL thinning was associated with a higher IOP range (-0.05 [95% CI, -0.06 to -0.03] μm per 1–mm Hg higher; P < .001), while a faster annual rate of RNFL thinning was associated with higher peak IOP (-0.05 [95% CI, -0.07 to -0.04] μm per 1–mm Hg higher; P < .001).

Factors including longer axial length, thicker central corneal thickness (CCT), history of filtration, surgery, history of laser trabeculoplasty, and presence of interim cataract surgery were additionally found to be associated with slower RNFL thinning over time In all multivariable models.

Data show IOP fluctuation (38.1%) had a higher contribution than mean IOP (17.8%) in a multivariate model. For the outcomes modeled using linear mixed regression, investigators found the adjusted R² was 0.113.

An accompanying editorial from Paul F. Palmberg, MD, PhD, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, noted the coundfounding flaw in the study, which investigators ackowledged, might ultimately negate the study's conclusions.

"Patient data were not censored for pressure values obtained after glaucomatous progression, when likely the medical treatment was increased to achieve a lower pressure with a consequently misleading appearance of greater overall variability," Palmberg said. "Risk factors should only be analyzed up to the point of an outcome."

Palmberg suggested the study investigators censor data for patients who underwent further treatment after progression to better determine the role of IOP variability.

The study, “Association of Intraocular Pressure with Retinal Nerve Fiber Layer Thinning in Patients with Glaucoma,” was published in JAMA Ophthalmology.