Pressure Variability Is an Independent Predictor of RNFL Thinning in Glaucoma

Higher intraocular pressure variability may foretell structural changes to the retina in individuals with glaucoma.

Intraocular pressure (IOP) variability is independently associated with the rate of retinal nerve fiber layer thinning (RNFL) in patients with glaucoma, supporting its potential use in clinical management, according to research published in JAMA Ophthalmology.

Researchers conducted a retrospective analysis of a longitudinal cohort to investigate the association of mean IOP and IOP variability with the rate of RNFL thinning in patients with glaucoma. 

The team enrolled patients from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation study, including eyes with at least 4 visits and 2 years of follow-up optical coherence tomography and IOP measurement. They used statistical modeling to test the association of IOP parameters with the rates of RNFL thinning and assessed the relative importance of the IOP parameters.

A total of 815 eyes (564 perimetric glaucoma and 251 preperimetric glaucoma) from 508 patients (mean age, 65.5±11.0 years; 55.1% women and 44.9% men) with imaging follow up for a mean of 6.3 years (range, 6.2-6.5). The cohort was 55.5% White, 38.4% Black, 4.7% Asian, and 1.6% other race/ethnicity. Overall, 64.8% of patients had self-reported hypertension, and 20.5% of patients had self-reported diabetes.

These results support the assessment of IOP variability as well as mean IOP in patients with glaucoma to identify those at greater risk of RNFL progression.

The researchers observed a mean rate of RNFL change of -0.67 μm/year (95% confidence interval [CI], -0.73 to -0.60). In multivariable models adjusted for mean IOP and other confounding factors, they found that faster annual rate of RNFL thinning was associated with higher variability in IOP (standard deviation, -0.20[ 95% CI, -0.26 to -0.15] μm/1-mm Hg higher; P <.001) or higher IOP range (-0.05 [95% CI, -0.06 to -0.03] μm/1-mm Hg higher; P <.001).

“IOP fluctuation and IOP range were more strongly associated with RNFL thinning compared with mean IOP in the present cohort,” the researchers report. “While the biological basis for this association is unknown, these results support the assessment of IOP variability as well as mean IOP in patients with glaucoma to identify those at greater risk of RNFL progression.”

Limitations of the study included participants with perimetric glaucoma predominantly composed of individuals with mild glaucoma, inclusion of patients who exhibited glaucomatous progression and may have been treated medically to achieve lower IOP, and no data on short-term IOP variability or the time that IOP was measured at each visit.

Disclosure: This research was supported by grants for participants’ glaucoma medications from Novartis/Alcon Laboratories, Allergan, Akorn, Pfizer, Merck, and Santen. The study authors have declared affiliations with the biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Nishida T, Moghimi S, Chang AC, et al. Association of intraocular pressure with retinal nerve fiber layer thinning in patients with glaucoma. JAMA Ophthalmol. Published online October 27, 2022. doi:10.1001/jamaophthalmol.2022.4462