Comparing the utility of retinal nerve fiber layer and ganglion cell inner plexiform layer OCT changes to detect glaucoma progression

Purpose: Measure and compare the rates of circumpapillary retinal nerve fiber layer (cpRNFL) and macular ganglion cell—inner plexiform layer (mGCIPL) thinning in glaucomatous eyes with and without visual field (VF) progression, across a broad range of disease severity, in a large clinical population.

Design: Retrospective, longitudinal study.

Participants: A total of 2464 eyes (1605 patients) with longitudinal testing (≥5 reliable cpRNFL, mGCIPL, and VF measurements). All cpRNFL and mGCIPL measurements were within 1 year of a VF test.

Methods: We used linear regression to measure rates of cpRNFL and mGCIPL thinning in suspect, mild, moderate, and advanced glaucoma (severity defined by Hodapp-Parrish-Anderson criteria). We compared thinning rates between eyes with and without VF progression (using trendor event-based criteria). Next, we used logistic mixedeffects models to estimate the impact of cpRNFL and mGCIPL thinning rates on the probability of VF progression. We used general linear hypothesis testing to assess the effect of cpRNFL and mGCIPL thinning rates in each stage of severity.

Main outcome measures: Rates of cpRNFL and mGCIPL thinning (μm/year) stratified by disease severity. Results: The cpRNFL and mGCIPL thinning rates were significantly faster in progressing eyes (—1.02 and —1.04 μm/year, respectively) than in nonprogressing eyes (—0.41 and —0.41 μm/year, respectively). Differences between progressors and nonprogressors diminished with worsening disease severity. The effect of cpRNFL and mGCIPL thinning on the probability of VF progression was similar overall (2.4% vs. 2.1% increased probability per 1 μm/year faster rate of thinning) but differed depending on the glaucoma severity. The effect of cpRNFL thinning was greatest in glaucoma suspects but was not statistically significant in advanced glaucoma. In contrast, the effect of mGCIPL thinning was smallest in suspects, increased with worsening disease severity, and was still statistically significant in advanced disease.

Conclusions: The cpRNFL and mGCIPL changes serve complementary roles in monitoring glaucoma progression depending on the stage of disease severity. The cpRNFL is more strongly associated with VF progression than mGCIPL in early glaucoma. The mGCIPL is more strongly associated with progression than cpRNFL in later stages of glaucoma.

Author(s): Alex T. Pham, Chris Bradley, Jithin Yohannan.

Journal: Ophthalmology

Doi: 10.1016/j.ophtha.2025.07.040

Link: https://www.aaojournal.org/article/S0161-6420(25)00485-3/fulltext

Clinical Paper of the Month manager: Nestor Ventura-Abreu

Editors in Chief: Francesco Oddone, Manuele Michelessi