Elsevier

Ophthalmology

Volume 127, Issue 10, October 2020, Pages 1322-1330
Ophthalmology

Original Article
Wide-field Trend-based Progression Analysis of Combined Retinal Nerve Fiber Layer and Ganglion Cell Inner Plexiform Layer Thickness: A New Paradigm to Improve Glaucoma Progression Detection

https://doi.org/10.1016/j.ophtha.2020.03.019Get rights and content

Objective

Evaluation of glaucoma progression with OCT has been centered on the analysis of progressive retinal nerve fiber layer (RNFL) thinning over the parapapillary region and/or progressive ganglion cell inner plexiform layer (GCIPL) thinning over the macula. We investigated (1) whether combining the RNFL and GCIPL as a single layer (i.e., RNFL-GCIPL) for wide-field progression analysis outperforms wide-field progression analysis of the RNFL or the GCIPL, and (2) whether eyes with progressive RNFL-GCIPL thinning are at risk of visual field (VF) progression.

Design

Prospective, longitudinal study.

Participants

A total of 440 eyes from 236 glaucoma patients; 98 eyes from 49 healthy individuals.

Methods

OCT RNFL/GCIPL/RNFL-GCIPL thickness and VF measurements were obtained at ∼4-month intervals for ≥3 years. Progressive changes of the RNFL/GCIPL/RNFL-GCIPL thicknesses were analyzed over a wide field (12×9 mm2) covering the parapapillary region and the macula with trend-based progression analysis (TPA) controlled at a false discovery rate of 5%. VF progression was determined by the Early Manifest Glaucoma Trial criteria.

Main Outcome Measures

Proportions of eyes with progressive RNFL/GCIPL/RNFL-GCIPL thinning; hazard ratios (HRs) for development of VF progression.

Results

More eyes showed progressive RNFL-GCIPL thinning (127 eyes; 28.9%, 95% confidence interval [CI]: 23.9%–33.8%) than progressive RNFL thinning (74 eyes; 16.8%, 95% CI: 13.1%–20.6%) and progressive GCIPL thinning (26 eyes; 5.9%, 95% CI: 3.7%–8.1%) in the glaucoma group over the study follow-up. Progressive RNFL-GCIPL thinning was almost always detected before or simultaneously with progressive RNFL thinning or progressive GCIPL thinning. The specificity of TPA (estimated from the healthy group) for detection of progressive RNFL-GCIPL thinning, progressive RNFL thinning, and progressive GCIPL thinning was 83.7% (95% CI: 74.9%–92.4%), 94.9% (95% CI: 90.6%–99.2%), and 96.9% (95% CI: 93.5%–100.0%), respectively. Eyes with progressive RNFL-GCIPL thinning had a higher risk to develop possible (HR: 2.4, 95% CI: 1.2–5.0) or likely (HR: 4.6, 95% CI: 1.5–14.0) VF progression, with adjustment of covariates, compared with eyes without progressive RNFL-GCIPL thinning.

Conclusions

Progression analysis of RNFL-GCIPL thickness reveals a significant portion of progressing eyes that neither progression analysis of RNFL thickness nor GCIPL thickness would identify. Wide-field progression analysis of RNFL-GCIPL thickness is effective to inform the risk of VF progression in glaucoma patients.

Section snippets

Subjects

A total of 236 glaucoma patients (229 patients [97.0%] with primary open-angle glaucoma; 7 patients [3.0%] with primary angle-closure glaucoma) and 49 healthy individuals were consecutively recruited from the glaucoma clinic and the general clinic in the Hong Kong Eye Hospital and the Chinese University of Hong Kong Eye Clinic between June 2015 and March 2016. Glaucoma was defined by the presence of narrowed neuroretinal rim and RNFL defects in clinical examination and OCT RNFL thickness

Trend-based Progression Analysis of RNFL-GCIPL Thickness Outperforms That of RNFL or GCIPL Thickness

A total of 5409 serial OCT images and 5345 serial VFs from 285 participants, including 440 eyes from 236 glaucoma patients and 98 eyes from 49 healthy participants who had been followed up at approximately 4-month intervals over 3.3±0.2 years (range, 3.0–3.7 years), were analyzed. Each eye had an average of 10.1 OCT scans (range, 4–13) and 9.9 VF tests (range, 4–13) for progression analysis. Table 1 compares the demographics and OCT and VF measurements between the diagnostic groups at the

Discussion

In this study, we integrate the RNFL and the GCIPL as a single layer (i.e., the RNFL-GCIPL) for progression analysis over a wide field (12×9 mm2) covering the parapapillary region and the macula, and demonstrate its importance for early detection of disease progression in glaucoma patients. With serial OCT and VF measurements obtained from 440 eyes of 236 glaucoma patients who had been followed up at ∼4-month intervals for at least 3 years, we show that progressive RNFL-GCIPL thinning often

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Financial Disclosure(s):

The authors made the following disclosures: C.L.: Speaker honorarium and research support – Carl Zeiss Meditec and Topcon; Patent – “Detection of disease-related retinal nerve fiber layer thinning” (U.S. Application No. 13/898,176); Patent license fees – Carl Zeiss Meditec.

Supported by the Hong Kong Research Grant Council General Research Fund 14101117; Topcon Research Foundation 2017–2018.

HUMAN SUBJECTS: Human subjects were included in this study. The study was conducted in accordance with the ethical standards stated in the 2013 Declaration of Helsinki, and approved by the Hong Kong Kowloon Central Research Ethics Committee, and obtained written informed consent.

No animal subjects were used in this study.

Author Contributions:

Conception and design: Leung

Data collection: Wu, Lin, Leung

Analysis and interpretation: Wu, Lin, Lam, Chan, Leung

Obtained funding: Leung

Overall responsibility: Wu, Lin, Lam, Chan, Leung

Drs Wu and Lin contributed equally to the manuscript.

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