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Editors Selection IGR 21-4

Risk factors: Is IOP variability a risk factor for structural damage?

Comment by Luciano Quaranta on:

106171 Association of Intraocular Pressure With Retinal Nerve Fiber Layer Thinning in Patients With Glaucoma, Nishida T; Moghimi S; Chang AC; Chang AC et al. et al., JAMA ophthalmology, 2022; 140: 1209-1216

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This is a retrospective longitudinal cohort study of patients with pre-perimetric and perimetric glaucoma who were enrolled in the Diagnostic Innovations in Glaucoma Study (DIGS) and African Descent and Glaucoma Evaluation Study (ADAGES). All DIGS and ADAGES participants were assessed longitudinally according to established protocols consisting of semiannual follow-up visits with clinical examination, imaging, and functional tests.

Aim of the study was to investigate the association of mean intraocular pressure and intraocular pressure variability (defined as the SD of intraocular pressure and the intraocular pressure range) with the rate of retinal nerve fiber layer thinning over time in patients with glaucoma.

Five hundred and eight glaucoma patients were included for the study (280 [55.1%] were female, 195 [38.4%] were African American, 24 [4.7%] were Asian, 281 [55.3%] were White, and eight [1.6%] were another race or ethnicity).The mean (SD) age was 65.5 (11.0) years. The mean rate of retinal nerve fiber layer change was ‐0.67 (95% CI, ‐0.73 to ‐0.60) µm per year. In multivariable models adjusted for mean intraocular pressure and other confounding factors, faster annual rate of retinal nerve fiber layer thinning was associated with a higher SD of intraocular pressure, long-term fluctuation (‐0.20 [95% CI, ‐0.26 to ‐0.15] µm per 1‐mmHg higher; P < .001) or higher intraocular pressure range (‐0.05 [95% CI, ‐0.06 to ‐0.03] µm per 1‐mmHg higher; P < .001).

The investigation has pointed out the importance of office-hours long-term IOP fluctuations for structural glaucoma progression in this cohort glaucoma patients with mild visual-field damage.

Results from prior studies on the association between long-term IOP variability and glaucomatous progression have been conflicting. The cause of these differences is not certain, but patients with glaucoma might be more susceptible to IOP variability, suggesting that IOP variability may have been more related to progression in patients with glaucoma.

IOP fluctuations play a crucial role in the progression of the disease, also in the early stages

On the basis of these results, it seems that IOP fluctuations play a crucial role in the progression of the disease, also in the early stages. From a clinical point of view, this observation underlies the role of an 'aggressive' IOP reduction and stabilization also in early and moderate glaucoma. For this reason I think that the paradigm 'the lower the better' could be applied also for the initial stages of the disease, adding also the concept of 'the most stable the better'.

Twenty-four-hour IOP and OCT studies would be desirable to have deeper insights in the pathogenesis of the disease.

I would like to congratulate the group of Dr Weinreb for another landmark paper in the field of glaucoma.

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