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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
  • Author Footnotes
    ∗ Drs Wu and Lin contributed equally to the manuscript.
    Ken Wu
    Footnotes
    ∗ Drs Wu and Lin contributed equally to the manuscript.
    Affiliations
    Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China
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  • Author Footnotes
    ∗ Drs Wu and Lin contributed equally to the manuscript.
    Chen Lin
    Footnotes
    ∗ Drs Wu and Lin contributed equally to the manuscript.
    Affiliations
    Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China
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  • Alexander Ka-Ngai Lam
    Affiliations
    Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China
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  • Leo Chan
    Affiliations
    Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China
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  • Christopher Kai-Shun Leung
    Correspondence
    Correspondence: Christopher Kai-Shun Leung, MD, MB ChB, Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China.
    Affiliations
    Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China
    Search for articles by this author
  • Author Footnotes
    ∗ Drs Wu and Lin contributed equally to the manuscript.

      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.

      Abbreviations and Acronyms:

      CI (confidence interval), GCIPL (ganglion cell inner plexiform layer), GPA (Guided Progression Analysis), HR (hazard ratio), IOP (intraocular pressure), MD (mean deviation), RGC (retinal ganglion cell), RNFL (retinal nerve fiber layer), TPA (trend-based progression analysis), VF (visual field)
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      References

        • Flaxman S.R.
        • Bourne R.R.A.
        • Resnikoff S.
        • et al.
        Global causes of blindness and distance vision impairment 1990-2020: a systematic review and meta-analysis.
        Lancet Glob Health. 2017; 5: e1221-e1234
        • Weinreb R.N.
        • Leung C.K.
        • Crowston J.G.
        • et al.
        Primary open-angle glaucoma.
        Nat Rev Dis Primers. 2016; 2: 16067
      1. Weinreb R.N. Garway-Heath D. Leung C.K. Consensus Series 8 – Progression of Glaucoma. Kugler Publications, Hague, Netherlands2011
        • Lee W.J.
        • Na K.I.
        • Ha A.
        • et al.
        Combined use of retinal nerve fiber layer and ganglion cell-inner plexiform layer event-based progression analysis.
        Am J Ophthalmol. 2018; 196: 65-71
        • Lee W.J.
        • Kim T.J.
        • Kim Y.K.
        • et al.
        Serial combined wide-field optical coherence tomography maps for detection of early glaucomatous structural progression.
        JAMA Ophthalmol. 2018; 136: 1121-1127
        • Lavinsky F.
        • Wu M.
        • Schuman J.S.
        • et al.
        Can macula and optic nerve head parameters detect glaucoma progression in eyes with advanced circumpapillary retinal nerve fiber layer damage?.
        Ophthalmology. 2018; 125: 1907-1912
        • Shin J.W.
        • Sung K.R.
        • Park S.W.
        Patterns of progressive ganglion cell-inner plexiform layer thinning in glaucoma detected by OCT.
        Ophthalmology. 2018; 125: 1515-1525
        • Hou H.W.
        • Lin C.
        • Leung C.K.
        Integrating macular ganglion cell inner plexiform layer and parapapillary retinal nerve fiber layer measurements to detect glaucoma progression.
        Ophthalmology. 2018; 125: 822-831
        • Hammel N.
        • Belghith A.
        • Weinreb R.N.
        • et al.
        Comparing the rates of retinal nerve fiber layer and ganglion cell-inner plexiform layer loss in healthy eyes and in glaucoma eyes.
        Am J Ophthalmol. 2017; 178: 38-50
        • Lee W.J.
        • Kim Y.K.
        • Park K.H.
        • et al.
        Trend-based analysis of ganglion cell-inner plexiform layer thickness changes on optical coherence tomography in glaucoma progression.
        Ophthalmology. 2017; 124: 1383-1391
        • Leung C.K.
        • Weinreb R.N.
        • Li Z.W.
        • et al.
        Long-term in vivo imaging and measurement of dendritic shrinkage of retinal ganglion cells.
        Invest Ophthalmol Vis Sci. 2011; 52: 1539-1547
        • Li Z.W.
        • Liu S.
        • Weinreb R.N.
        • et al.
        Tracking dendritic shrinkage of retinal ganglion cells after acute elevation of intraocular pressure.
        Invest Ophthalmol Vis Sci. 2011; 52: 7205-7212
        • Yu M.
        • Lin C.
        • Weinreb R.N.
        • et al.
        Risk of visual field progression in glaucoma patients with progressive retinal nerve fiber layer thinning: a 5-year prospective study.
        Ophthalmology. 2016; 123: 1201-1210
        • Lin C.
        • Mak H.
        • Yu M.
        • et al.
        Trend-based progression analysis for examination of the topography of rates of retinal nerve fiber layer thinning in glaucoma.
        JAMA Ophthalmol. 2017; 135: 189-195
      2. Weinreb R.N. Garway-Heath D.F. Leung C.K. Diagnosis of Primary Open Angle Glaucoma, Consensus Series – 10. Kugler Publications, Hague, Netherlands2017
        • Heijl A.
        • Leske M.C.
        • Bengtsson B.
        • et al.
        • EMGT Group
        Measuring visual field progression in the Early Manifest Glaucoma Trial.
        Acta Ophthalmol Scand. 2003; 81: 286-293
        • Yang Z.
        • Sun X.
        • Hardin J.W.
        A note on the tests for clustered matched-pair binary data.
        Biom J. 2010; 52: 638-652
        • Obuchowski N.A.
        On the comparison of correlated proportions for clustered data.
        Stat Med. 1998; 17: 1495-1507
        • Connor R.J.
        Sample size for testing differences in proportions for the paired-sample design.
        Biometrics. 1987; 43: 207-211
        • Leung C.K.
        • Yu M.
        • Weinreb R.N.
        • et al.
        Retinal nerve fiber layer imaging with spectral-domain optical coherence tomography: a prospective analysis of age-related loss.
        Ophthalmology. 2012; 119: 731-737
        • Leung C.K.
        • Ye C.
        • Weinreb R.N.
        • 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

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