Detecting glaucoma progression based on multiple retinal layers' thickness

Thinning of the circumpapillary retinal nerve fiber layer (cpRNFL) and the macular ganglion cell–inner plexiform layer (mGCIPL) is associated with progression of glaucoma at different stages of the disease, according to Alex T. Pham, MD, and coauthors, who published their findings in Ophthalmology.¹

He is from the Department of Ophthalmology and Visual Sciences, University of Maryland School of Medicine, Baltimore. Coauthors Chris Bradley, PhD, and Jithin Yohannan, MD, MPH, are, respectively, from the Wilmer Eye Institute, Johns Hopkins University School of Medicine, and the Wilmer Eye Institute and the Malone Center for Engineering in Healthcare, Johns Hopkins University.

Their study represents a step forward in investigations of the retinal layers as they are affected by glaucoma in that it looked at the rates of thinning in patients with progression of glaucoma compared with patients without progression and included patients with all degrees of glaucoma severity.

Their goal, they explained, was to identify which structural measure is more associated with progression at each stage of glaucoma; this knowledge will “help clinicians optimize disease monitoring in patient populations with varying disease severity and improve earlier detection of progression,” they commented.

“To date,” they said, “studies comparing rates of cpRNFL thinning and mGCIPL thinning in glaucoma progression are limited by modest sample sizes, focus primarily on a single stage of disease (early glaucoma or advanced glaucoma), or do not differentiate stages of disease severity.^2-8

Study methodology

Pham and colleagues conducted a large retrospective longitudinal study that included 2464 eyes of 1605 patients who had undergone testing over time, ie, five or more reliable cpRNFL, mGCIPL, and visual field measurements. All measurements of the cpRNFL and mGCIPL were obtained within 1 year of a visual field test, they recounted.

The authors used linear regression analysis to determine the rates of cpRNFL and mGCIPL thinning in glaucoma suspects and those with mild, moderate, and advanced glaucoma.

They then compared the rates of thinning in eyes with and without visual field progression, estimated the impact of cpRNFL and mGCIPL rates of thinning on the probability of visual field progression, and assessed the effect of the rates of cpRNFL and mGCIPL thinning in each stage of glaucoma severity, they explained.

The main study outcomes were the rates of cpRNFL and mGCIPL thinning expressed in microns per year stratified by disease severity.

What new information on the impact of thinning did the investigators uncover?

Pham and colleagues reported that the rates of thinning of the cpRNFL and mGCIPL were significantly faster in eyes in which the visual field damage was progressing (–1.02 and –1.04 μm/year, respectively) compared with eyes in which there was no progression (–0.41 and –0.41 μm/year, respectively).

They commented, “The differences between progressors and nonprogressors diminished with worsening disease severity. The effect of cpRNFL and mGCIPL thinning on the probability of visual field progression was similar overall, ie, 2.4% vs. 2.1% increased probability per 1 μm/year faster rate of thinning but differed depending on the glaucoma severity.”

They also found that the effect of cpRNFL thinning was greatest in glaucoma suspects but was not significant in patients with advanced glaucoma. In contrast, the effect of mGCIPL thinning was the smallest in glaucoma suspects, increased with worsening disease severity, and was still significant in patients with advanced disease.

The authors said, “Our study reinforces that faster rates of cpRNFL and mGCIPL thinning are associated with visual field progression in glaucoma. Of note, we observed that the strength of the association between thinning rates and progression varies with the disease severity. cpRNFL thinning is most relevant in the early stages of glaucoma, whereas mGCIPL thinning becomes more relevant in later disease stages. Our findings highlight the complementary roles of cpRNFL and mGCIPL metrics in understanding glaucoma progression and underscore the need for disease stage-specific approaches to monitoring progression with these structural measures.”

References

1. Pham AT, Bradley C, Yohannan J. Comparing the utility of retinal nerve fiber layer and ganglion cell inner plexiform layer OCT changes to detect glaucoma progression. Ophthalmology. 2026;133:12-23. https://www.aaojournal.org/article/S0161-6420(25)00485-3/fulltext

2. Shin JW, Sung KR, Lee GC, et al. Ganglion cell-inner plexiform layer change detected by optical coherence tomography indicates progression in advanced glaucoma. Ophthalmology. 2017;124:1466-1474.

3. Naghizadeh F, Garas A, Vargha P, et al. Detection of early glaucomatous progression with different parameters of the RTVue optical coherence tomograph.J Glaucoma. 2014;23:195-198

4. Sung KR, Sun JH, Na JH, et al. Progression detection capability of macular thickness in advanced glaucomatous eyes. Ophthalmology. 2012; 119:308-313.

5. Shin JW, Sung KR, Song MK. Ganglion cell-inner plexiform layer and retinal nerve fiber layer changes in glaucoma suspects enable prediction of glaucoma development. Am J Ophthalmol. 2020; 210:26-34.

6. Na JH, Sung KR, Baek S, et al. Detection of glaucoma progression by assessment of segmented macular thickness data obtained using spectral domain optical coherence tomography. Invest Ophthalmol Vis Sci. 2012; 53:3817-3826.

7. Leung CKS, Ye C, Weinreb RN, et al. Impact of age-related change of retinal nerve fiber layer and macular thicknesses on evaluation of glaucoma progression. Ophthalmology. 2013;120:2485-2492.

8. Na JH, Sung KR, Lee JR, et al. Detection of glaucomatous progression by spectral-domain optical coherence tomography. Ophthalmology. 2013;120:1388-1395.