Higher Risk of Developing Glaucoma Linked to Faster Rates of GCIPL Thinning

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Rates of change measured via macular OCT may prove beneficial for monitoring the progression of glaucoma in eyes with suspected glaucoma.

A faster rate of ganglion cell/inner plexiform layer (GCIPL) and circumpapillary retinal nerve fiber layer (cpRNFL) thinning was associated with a higher risk of developing perimetric glaucoma in eyes with suspected glaucoma in new research.1

Study investigators from the Shiley Eye Institute cited the rate of GCIPL thinning as 2 times faster in eyes with suspected glaucoma that developed perimetric glaucoma compared with eyes that did not, suggesting the greater importance of evaluation in clinical practice.

“It is clinically important to diagnose the development of perimetric glaucoma early in eyes with suspected glaucoma to reduce the progression of the disease with appropriate treatment,” wrote the investigative team, led by Robert N. Weinreb, MD, University of California, San Diego.

Glaucomatous damage to the macular could occur in the early stages of glaucoma, highlighting the importance of damage assessment for both diagnosis and monitoring. Previous findings from Weinreb and colleagues dictated an association between faster rates of cpRNFL thinning and an increased risk of glaucomatous visual field defects in eyes with suspected glaucoma.

The current longitudinal cohort study collected data in December 2021 from patients with suspected glaucoma enrolled in the USCD-based Diagnostic Innovations in Glaucoma Study (DIGS) and the multicenter African Descent and Glaucoma Evaluation Study (ADAGES). Based on this data, the study looked to predict the probability of glaucoma development using rates of change measured via optical coherence tomography (OCT).

To be considered as having suspected glaucoma, eyes were required to have elevated intraocular pressure (≥22 mm Hg) or glaucomatous-appearing optic discs without the presence of repeatable glaucomatous visual field damage. Eyes were additionally required to have 2 year or longer follow-up with 3 or more macular SD-OCT scans. The development of perimetric glaucoma was defined as having 3 consecutive results showing abnormal visual fields.

In analysis, linear mixed-effects models compared rates of change of global, minimum, and sectoral GCIPL between eyes with suspected glaucoma that did and did not develop perimetric glaucoma. Joint longitudinal survival analyses were used to investigate the association between GCIPL thickness measurements and the development of perimetric glaucoma.

The study enrolled a total of 658 eyes with suspected glaucoma from 462 patients with a mean of 5.5 OCT-imaging tests and a mean follow-up of 3.2 years. Among the study population, 153 eyes (117 patients, 23%) developed perimetric glaucoma during the follow-up. Investigators found that both globally and for most of the sectors, the rates of GCIPL thinning were significantly faster in eyes with suspected glaucoma that developed perimetric glaucoma.

When comparing eyes with suspected glaucoma that did not develop and did develop perimetric glaucoma, data showed the mean rates of GCIPL thinning were −0.66 μm/y (95% CI, −0.91 to −0.40) and −1.28 μm/y (95% CI, -1.65 to -0.90), respectively, (difference, –0.62 μm/y; 95% CI, −1.07 to −0.16; P = .02).

The results from the joint longitudinal survival model revealed every 1-μm/y faster rate of minimum GCIPL was significantly associated with a 2.4-times higher risk of developing perimetric glaucoma and a 1.9-times higher risk for every 1 μm/y faster rate of global cpRNFL thinning (HR, 2.4; 95% CI, 1.8 to 3.2, and HR, 1.99; 95% CI, 1.76 to 2.22, respectively; P < .001).

Among the covariates of interest, African American race, male sex, 1-dB higher baseline visual field pattern standard deviation, and 1-mm Hg higher mean IOP during follow-up were each associated with a higher risk of developing perimetric glaucoma.

Investigators noted the mean follow-up time was significantly higher for eyes that developed perimetric glaucoma, compared to those that did not, meaning the group had sufficient data to efficiently represent the course of the disease.

“The number of IOP-lowering medications was significantly higher in eyes with suspected glaucoma that developed perimetric glaucoma compared with eyes that did not develop it,” they wrote. “In other words, despite having more intensive treatment, the group of eyes with suspected glaucoma still developed perimetric glaucoma with sufficient follow-up time.”


  1. Mohammadzadeh V, Moghimi S, Nishida T, et al. Association of Rates of Ganglion Cell and Inner Plexiform Thinning With Development of Glaucoma in Eyes With Suspected Glaucoma. JAMA Ophthalmol. Published online March 02, 2023. doi:10.1001/jamaophthalmol.2023.0005