Longitudinal Variability of Optic Disc and Retinal Nerve Fiber Layer Measurements

Leung, Christopher Kai-Shun; Cheung, Carol Y.; Lin, D.; Pang, Chi Pui; Lam, Dennis Shun Chiu; Weinreb, Robert N.

doi:10.1167/iovs.07-1187

Cited by 67 publications

(64 citation statements)

References 29 publications

(23 reference statements)

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“…4 In a clinical setting, children who have mild glaucoma or advanced (largely stable) glaucoma showed high reproducibility for OCT measurements of total macular volume and average RNFL thickness over three measurements spanning an average of 4.3 years. Just as one study in an adult population found that longitudinal variability in OCT measures did not change with the severity of glaucoma, 16 we found that in children OCT measurements were reproducible for those with a history of elevated IOP. High reproducibility in our sample of children with a history of elevated IOP may be attributable to the fact that only 1 patient (who was in the advanced glaucoma group) had progression in their disease during the study period.…”

Section: Discussionsupporting

confidence: 59%

“…[13][14][15] In any event, axial length growth would still likely be <1.0 mm over the course of 3 to 4 years; the average RNFL decline of 2.2 μm attributable an axial length growth of 1.0 mm would still fall within the variance of 9.3 μm 2 for this variable in the present study and other adult published studies. 4 In a clinical setting, children who have mild glaucoma or advanced (largely stable) glaucoma showed high reproducibility for OCT measurements of total macular volume and 16 we found that in children OCT measurements were reproducible for those with a history of elevated IOP. High reproducibility in our sample of children with a history of elevated IOP may be attributable to the fact that only 1 patient (who was in the advanced glaucoma group) had progression in their disease during the study period.…”

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confidence: 64%

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Longitudinal reproducibility of optical coherence tomography measurements in children

Prakalapakorn¹,

Freedman²,

Holgado³

et al. 2011

Journal of American Association for Pediatric Ophthalmology and

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Purpose-To evaluate the longitudinal reproducibility of optical coherence tomography (OCT) measurements in normal and glaucomatous eyes of children.Methods-In this two-setting prospective study, OCT-3 was used to obtain fast retinal nerve fiber layer (RNFL) and of macular thickness scans. In the first study setting, the normal eyes of healthy children were scanned on presentation, at 2 weeks, and 3 years, with axial length measured at the first and last examinations. In the second setting, OCT scans of patients in the pediatric glaucoma clinic were performed over 4 years as clinically indicated. Eyes were classified as "normal," (normal eyes and those with physiologic cupping but normal intraocular pressure (IOP)); "mild glaucoma" (elevated IOP and a normal optic nerve appearance); or "advanced glaucoma,"(severe cupping or progressive glaucoma). Intraclass correlation coefficients (ICC) were used to evaluate the reproducibility of measurements on the same day and over time.Results-In the first setting, 8 normal eyes were included. Axial length increased 0.11 ± 0.04 mm/year over an average of 3.3 years (P = 0.03); there was no statistically significant change in RNFL thickness (P = 0.30). In our second setting, 27 normal eyes and 37 eyes with glaucoma were included. ICCs across the three visits for total macular volume were 0.80-0.91 and for average RNFL were 0.73-0.95. Conclusions-GlobalOCT measurements in children were reproducible over years and were not affected by normal increase in axial length. OCT shows promise as an objective tool for longitudinal assessment of children.Monitoring children with known or suspected glaucoma often poses a challenge to the clinician due to the difficulty of obtaining reliable visual fields and other objective measures of disease progression or stability. Optical coherence tomography (OCT) is a fast, noninvasive imaging technology that can measure the retinal nerve fiber layer (RNFL) Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. OCT measurements of RNFL and macular thickness differ in normal and glaucomatous eyes of children. 5 OCT measurements of both RNFL and macular thickness have also been shown to correlate negatively with increasing grade of glaucomatous damage seen on optic nerve head stereophotographs. 6 In order for OCT to be useful in monitoring children with glaucoma for disease progression, it must be reproducible over time despite normal axial length growth. Previous studies have shown that in healthy eyes of children, OCT measurements of macular and RNFL thickness are reproducible within the same day 7 ; however...

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Section: Discussionsupporting

confidence: 59%

mentioning

confidence: 64%

Longitudinal reproducibility of optical coherence tomography measurements in children

Prakalapakorn¹,

Freedman²,

Holgado³

et al. 2011

Journal of American Association for Pediatric Ophthalmology and

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“…The medians of VCC, ECC, and OCT SDRES values in this study are similar to previous estimates of short-and long-term RNFLT variability measured by VCC, ECC, and OCT in glaucoma suspects and control subjects. [44][45][46] In order to highlight how well these devices can detect clinically relevant RNFLT change over time, a simple model was derived. A linear decrease of RNFLT from the median baseline measurement in control subjects to that of glaucoma patients within 10 years was considered a meaningful rate of RNFLT change.…”

Section: Discussionmentioning

confidence: 99%

“…This is largely consistent with previous research on the longitudinal reproducibility of VCC and OCT RNFLT. 45 The birefringent properties of the cornea do not change significantly over time, 47 hence atypical retardance measurements also should not change. The TSS identifies atypical retardance patterns, 27 hence changes in TSS may be predictive of spurious rates of RNFLT change.…”

Section: Discussionmentioning

confidence: 99%

Rates of retinal nerve fibre layer thickness change in glaucoma patients and control subjects

O’Leary

Artes

Hutchison

et al. 2012

Eye

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Purpose To examine the rates of retinal nerve fibre layer thickness (RNFLT) change in glaucoma patients and healthy, age-similar control subjects with three techniques: scanning laser polarimetry with variable corneal compensation (VCC) and enhanced corneal compensation (ECC), and timedomain optical coherence tomography (OCT). Methods Sixty-one patients and thirty-three controls were examined with each technique and with standard automated perimetry (SAP) every 6 months. Rates of global RNFLT change and SAP mean deviation (MD) change were estimated with linear mixedeffects models. Results The median (interquartile range) baseline age was 64.4 (58.2, 71.0) years for patients and 62.4 (56.3, 70.1) years for controls (P ¼ 0.56). There was a median of seven examinations over 3.1 years for patients and six examinations in 3.0 years for controls. Baseline visual field MD and RNFLT for all imaging modalities were significantly lower (Po0.01) in patients compared with controls. Rates of RNFLT change were not significantly different between patients and controls (PZ0.19). Mean rates of VCC-measured RNFLT change were À 0.18 and À 0.37 lm per year in patients and controls, whereas the respective figures for ECC and OCT were À 0.13 and À 0.31 lm per year, and 0.04 and 0.61 lm per year. Mean rates of MD change were À 0.20 and 0.03 dB per year in patients and controls, respectively (P ¼ 0.01). Conclusion Rates of RNFLT change in glaucoma patients were not statistically different from control subjects for any modality. A significantly negative rate of MD change in patients suggests a genuine, continued deterioration in these patients not reflected by RNFLT changes.

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“…45 The sources of measurement variability for VF tests include neural noise, variation in cognitive function (such as fatigue) and in decision criteria, learning effects, distractions in the test environment and the effect of technician instructions to patients. 8,[46][47][48][49][50] The sources of measurement variability in OCT imaging include media opacity and other causes of poor signal strength, [51][52][53] eye movement, scan misalignment (particularly for TD OCT) and software errors in image segmentation. 54,55 When a cohort is followed with VF testing and imaging, agreement on the eyes demonstrating glaucomatous progression is poor (for the most part, different eyes are identified as progressing by structure and function).…”

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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Longitudinal Variability of Optic Disc and Retinal Nerve Fiber Layer Measurements

Cited by 67 publications

References 29 publications

Longitudinal reproducibility of optical coherence tomography measurements in children

Longitudinal reproducibility of optical coherence tomography measurements in children

Rates of retinal nerve fibre layer thickness change in glaucoma patients and control subjects

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

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