Impact of Age-related Change of Retinal Nerve Fiber Layer and Macular Thicknesses on Evaluation of Glaucoma Progression

Leung, Christopher Kai-Shun; Ye, Cong; Weinreb, Robert N.; Yu, Marco; Lai, Gilda; Lam, Dennis Shun Chiu

doi:10.1016/j.ophtha.2013.07.021

Cited by 150 publications

(119 citation statements)

References 29 publications

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“…In accordance with Leung et al 5 and Wang et al, 9 no difference of mINL/OPL thickness between normalRNFLs and glaucoma patients was found. This seems contradictory to our finding of an inverse correlation of mGCL/IPL thickness and mINL/OPL thickness.…”

Section: Discussionsupporting

confidence: 89%

“…4 Studies found that the mGCL and inner plexiform layer (IPL), the macular ganglion cell complex (mGCC = RNFL + GCL + IPL), and the total macular thickness can be used to detect glaucoma progression. 5,6 Less explored is the effect of glaucoma on deeper retinal layers. It was found that glaucoma might be associated with changes at the level of photoreceptors.…”

mentioning

confidence: 99%

“…It was found that glaucoma might be associated with changes at the level of photoreceptors. 7,8 The involvement of the inner nuclear layer is not clear: Some have reported that outer retinal layer thickness and inner nuclear layer thickness is not changed from glaucoma 5,9 while others have found a thinning of the inner nuclear layer. 10 Recent works from nonglaucomaassociated optic neuropathies showed that optic neuropathy may lead to thickening and edema in the inner nuclear layer, which was termed microcystic macular edema (MME).…”

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confidence: 99%

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Retrograde Maculopathy in Patients With Glaucoma

Brazerol

Iliev

Höhn

et al. 2017

Journal of Glaucoma

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Purpose: Macular optical coherence tomography (OCT) analysis can be used for quantitative measures of optic nerve atrophy at a location far from the optic nerve head. This recently led to the finding of microcystic macular edema (MME), that is vacuolar inclusions in the macular inner nuclear layer, in some glaucoma patients. The involvement of individual retinal layers is yet unclear in glaucoma. In this study we systematically investigated glaucoma-induced changes in macular layers to evaluate whether glaucoma-associated damage extends beyond the macular ganglion cell layer. Patients and Methods:We included 218 consecutive patients and 282 eyes with confirmed primary open-angle glaucoma or pseudoexfoliation glaucoma, and macular OCT in a cross-sectional observational study. Eyes were screened for presence of MME. Thickness of individual retinal layers was determined using a semiautomatic segmentation algorithm. Peripapillary nerve fiber layer thickness and mean defect in visual field testing were extracted from OCT and medical records, respectively. Results were compared with a small group of eyes with no apparent glaucoma.Results: We found MME in 5 eyes from 5 primary open-angle glaucoma patients and 3 eyes of 3 pseudoexfoliation glaucoma patients (2.8%). MME was confined to the inner nuclear layer in a perifoveal ring and was associated with thinning of the ganglion cell layer and thickening of the macular inner nuclear layer. Glaucoma eyes without MME showed a significant inverse correlation of inner nuclear layer thickness with glaucoma severity.Conclusions: Glaucomatous damage leads to a gradual thickening of the inner nuclear layer, which leads to MME in more severe glaucoma cases. These changes, along with nerve fiber loss and ganglion cell loss, may be summarized as glaucoma-associated retrograde maculopathy.

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Section: Discussionsupporting

confidence: 89%

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confidence: 99%

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confidence: 99%

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Retrograde Maculopathy in Patients With Glaucoma

Brazerol

Iliev

Höhn

et al. 2017

Journal of Glaucoma

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“…13,22 Imaging-based quantitative measurements have diagnostic utility [23][24][25][26][27][28][29] and numerous publications support the ability of imaging-based measurements to identify glaucoma deterioration. [30][31][32][33][34][35][36][37][38][39][40] Progressive structural change has been shown to be useful as a predictor of subsequent VF loss. 41,42 The ability of imaging to detect deterioration has been compared with that of VF testing, controlling for the false-positive rate of the chosen progression criteria.…”

Section: Trial Registrationmentioning

confidence: 99%

Combining optical coherence tomography with visual field data to rapidly detect disease progression in glaucoma: a diagnostic accuracy study

Garway-Heath

Zhu

Qian

et al. 2018

Health Technol Assess

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Background Progressive optic nerve damage in glaucoma results in vision loss, quantifiable with visual field (VF) testing. VF measurements are, however, highly variable, making identification of worsening vision (‘progression’) challenging. Glaucomatous optic nerve damage can also be measured with imaging techniques such as optical coherence tomography (OCT). Objective To compare statistical methods that combine VF and OCT data with VF-only methods to establish whether or not these allow (1) more rapid identification of glaucoma progression and (2) shorter or smaller clinical trials. Design Method ‘hit rate’ (related to sensitivity) was evaluated in subsets of the United Kingdom Glaucoma Treatment Study (UKGTS) and specificity was evaluated in 72 stable glaucoma patients who had 11 VF and OCT tests within 3 months (the RAPID data set). The reference progression detection method was based on Guided Progression Analysis™ (GPA) Software (Carl Zeiss Meditec Inc., Dublin, CA, USA). Index methods were based on previously described approaches [Analysis with Non-Stationary Weibull Error Regression and Spatial enhancement (ANSWERS), Permutation analyses Of Pointwise Linear Regression (PoPLR) and structure-guided ANSWERS (sANSWERS)] or newly developed methods based on Permutation Test (PERM), multivariate hierarchical models with multiple imputation for censored values (MaHMIC) and multivariate generalised estimating equations with multiple imputation for censored values (MaGIC). Setting Ten university and general ophthalmology units (UKGTS) and a single university ophthalmology unit (RAPID). Participants UKGTS participants were newly diagnosed glaucoma patients randomised to intraocular pressure-lowering drops or placebo. RAPID participants had glaucomatous VF loss, were on treatment and were clinically stable. Interventions 24-2 VF tests with the Humphrey Field Analyzer and optic nerve imaging with time-domain (TD) Stratus OCT™ (Carl Zeiss Meditec Inc., Dublin, CA, USA). Main outcome measures Criterion hit rate and specificity, time to progression, future VF prediction error, proportion progressing in UKGTS treatment groups, hazard ratios (HRs) and study sample size. Results Criterion specificity was 95% for all tests; the hit rate was 22.2% for GPA, 41.6% for PoPLR, 53.8% for ANSWERS and 61.3% for sANSWERS (all comparisons p ≤ 0.042). Mean survival time (weeks) was 93.6 for GPA, 82.5 for PoPLR, 72.0 for ANSWERS and 69.1 for sANSWERS. The median prediction errors (decibels) when the initial trend was used to predict the final VF were 3.8 (5th to 95th percentile 1.7 to 7.6) for PoPLR, 3.0 (5th to 95th percentile 1.5 to 5.7) for ANSWERS and 2.3 (5th to 95th percentile 1.3 to 4.5) for sANSWERS. HRs were 0.57 [95% confidence interval (CI) 0.34 to 0.90; p = 0.016] for GPA, 0.59 (95% CI 0.42 to 0.83; p = 0.002) for PoPLR, 0.76 (95% CI 0.56 to 1.02; p = 0.065) for ANSWERS and 0.70 (95% CI 0.53 to 0.93; p = 0.012) for sANSWERS. Sample size estimates were not reduced using methods including OCT data. PERM hit rates were between 8.3% and 17.4%. Treatment effects were non-significant in MaHMIC and MaGIC analyses; statistical significance was altered little by incorporating imaging. Limitations TD OCT is less precise than current imaging technology; current OCT technology would likely perform better. The size of the RAPID data set limited the precision of criterion specificity estimates. Conclusions The sANSWERS method combining VF and OCT data had a higher hit rate and identified progression more quickly than the reference and other VF-only methods, and produced more accurate estimates of the progression rate, but did not increase treatment effect statistical significance. Similar studies with current OCT technology need to be undertaken and the statistical methods need refinement. Trial registration Current Controlled Trials ISRCTN96423140. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 4. See the NIHR Journals Library website for further project information. Data analysed in the study were from the UKGTS. Funding for the UKGTS was provided through an unrestricted investigator-initiated research grant from Pfizer Inc. (New York, NY, USA), with supplementary funding from the NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK. Imaging equipment loans were made by Heidelberg Engineering, Carl Zeiss Meditec and Optovue (Fremont, CA, USA). Pfizer, Heidelberg Engineering, Carl Zeiss Meditec and Optovue had no input into the design, conduct, analysis or reporting of any of the UKGTS findings or this work. The sponsor for both the UKGTS and RAPID data collection was Moorfields Eye Hospital NHS Foundation Trust. David F Garway-Heath, Tuan-Anh Ho and Haogang Zhu are partly funded by the NIHR Biomedical Research Centre based at Moorfields Eye Hospital and UCL Institute of Ophthalmology. David F Garway-Heath’s chair at University College London (UCL) is supported by funding from the International Glaucoma Association.

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“…Der Einfluss des Altersverlustes auf OCT-Verlaufsmessungen scheint für RNF geringer ausgeprägt zu sein als für die Makulaschichtdickenmessung (s. unten). So konnten Leung et al[9] in einer Glaukomgruppe im Ver-Abb. 2 8 Zirkumpapillärer B-Scan eines Auges mit Segmentierung der retinalen Nervenfaserschicht (dunkel) und Vergleich der Schichtdickenwerte der Messung mit der Normalpopulation.…”

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