BACKGROUND/AIMS—To determine the reproducibility of the Humphrey optical coherence tomography scanner (OCT), software version 5.0, for measurement of retinal nerve fibre layer (RNFL) thickness in normal subjects and to compare OCT measurements with published histological thickness of the human RNFL.
METHODS—Three independent measurements were obtained at each session for one eye from 15 normal subjects with a mean age of 30.8 (SD 10.9) years. Scans were taken in the peripapillary retina using the default setting (1.74 mm radius from centre of the optic disc) and were repeated 1 week later. Additional scans were obtained at the optic nerve head (ONH) margin overlying the scleral rim, for comparison with available histological data on the human RNFL.
RESULTS—For the 1.74 mm circular scan, the mean coefficient of variation (COV) for the global RNFL thickness measurement was 5% (SD 3%). This increased to 8% (3%) for quadrant measurements and to 9% (3%) with further subdivision into 12 segments. Significant differences (p<0.05) between sessions were only found when the data were divided into segments. The mean RNFL thickness for the 1.74 mm scan was 127.87 (9.81) µm. The RNFL was maximal at the superior disc pole, 161.44 µm (14.8), and minimal at the temporal pole, 83.1 (12.8) µm. Peak thickness values occurred superior temporal and inferior temporal to the vertical axis. RNFL thickness for every sector of the disc was greatest at the margin of the optic disc (mean 185.79 µm; SD 32.61). Although the variation in RNFL thickness around the disc follows published histology data, the OCT underestimates RNFL thickness by an average of 37% (SD 11; range 21-48%).
CONCLUSION—The OCT provides reproducible measurement of the retinal structures that are consistent with the properties of the RNFL. However, comparison with available studies of RNFL thickness in the human suggests that in its present form, the OCT underestimates RNFL thickness. Further refinement of this technology is required to improve the accuracy with which the OCT measures retinal nerve fibre layer thickness.
While it is often said that structural damage due to glaucoma precedes functional damage, it is not always clear what this statement means. This review has two purposes: first, to show that a simple linear relationship describes the data relating a particular functional test (standard automated perimetry (SAP)) to a particular structural test (optical coherence tomography (OCT)); and, second, to propose a general framework for relating structural and functional damage, and for evaluating if one precedes the other. The specific functional and structural tests employed are described in Section 2. To compare SAP sensitivity loss to loss of the retinal nerve fiber layer (RNFL) requires a map that relates local field regions to local regions of the optic disc as described in Section 3. When RNFL thickness in the superior and inferior arcuate sectors of the disc are plotted against SAP sensitivity loss (dB units) in the corresponding arcuate regions of the visual field, RNFL thickness becomes asymptotic for sensitivity losses greater than about 10 dB. These data are well described by a simple linear model presented in Section 4. The model assumes that the RNFL thickness measured with OCT has two components. One component is the axons of the retinal ganglion cells and the other, the residual, is everything else (e.g. glial cells, blood vessels). The axon portion is assumed to decrease in a linear fashion with losses in SAP sensitivity (in linear units); the residual portion is assumed to remain constant. Based upon severe SAP losses in anterior ischemic optic neuropathy (AION), the residual RNFL thickness in the arcuate regions is, on average, about one-third of the premorbid (normal) thickness of that region. The model also predicts that, to a first approximation, SAP sensitivity in control subjects does not depend upon RNFL thickness. The data (Section 6) are, in general, consistent with this prediction showing a very weak correlation between RNFL thickness and SAP sensitivity. In Section 7, the model is used to estimate the proportion of patients showing statistical abnormalities (worse than the 5th percentile) on the OCT RNFL test before they show abnormalities on the 24-2 SAP field test. Ignoring measurement error, the patients with a relatively thick RNFL, when healthy, will be more likely to show significant SAP sensitivity loss before statistically significant OCT RNFL loss, while the reverse will be true for those who start with an average or a relatively thin RNFL when healthy. Thus, it is important to understand the implications of the wide variation in RNFL thickness among control subjects. Section 8 describes two of the factors contributing to this variation, variations in the position of blood vessels and variations in the mapping of field regions to disc sectors. Finally, in Sections 7 and 9, the findings are related to the general debate in the literature about the relationship between structural and functional glaucomatous damage and a framework is proposed for understanding what is meant by the question, ‘Does structural damage precede functional damage in glaucoma?’ An emphasis is placed upon the need to distinguish between “statistical” and “relational” meanings of this question.
To compare the functional changes in visual fields with optical coherence tomography (OCT) findings in patients with ocular hypertension, open angle glaucoma, and suspected glaucoma. In addition, our purpose is to evaluate the correlation of global indices with the structural glaucomatous defect, to assess their statistical importance in all the groups of our study, and to estimate their validity to the clinical practice.
One hundred sixty nine eyes (140 patients) were enrolled. The patients were classified in three groups. Group 1 consisted of 54 eyes with ocular hypertension, group 2 of 42 eyes with preperimetric glaucoma, and group 3 of 73 eyes with chronic open angle glaucoma. All of them underwent ophthalmic examination according to a prefixed protocol, OCT exam (Stratus 3000) for retinal nerve fiber layer (RNFL) thickness measurement with fast RNFL thickness protocol and visual fields (VF) examination with Octopus perimeter (G2 program, central 30–2 threshold strategy). Pearson correlation was calculated between RNFL thickness and global index of VF.
A moderate correlation between RNFL thickness and indices mean sensitivity (MS), mean defect (MD) and loss variance (LV) of VF (0.547, −0.582, −0.527, respectively; P <0.001) was observed for all patients. Correlations of the ocular hypertension and preperimetric groups are weak. Correlation of RNFL thickness with global indices becomes stronger as the structural alterations become deeper in OCT exam. Correlation of RNFL thickness with the global index of VF, in respective segments around optic disk was also calculated and was found significant in the nasal, inferior, superior, and temporal segments.
RNFL average thickness is not a reliable index for early diagnosis of glaucoma and for the follow-up of patients with ocular hypertension. Segmental RNFL thickness seems to be a more reliable index. Deep structural alterations with OCT examination constitute an important indication of early functional changes, even if they are not still detected with achromatic perimetry. The MD index of VF seems to be more sensitive for the follow-up of patients with ocular hypertension.
glaucoma; ocular hypertension; OCT; visual fields; RNFL thickness
To determine the agreement between peripapillary retinal nerve fiber layer (RNFL) thickness measurements from Stratus time domain optical coherence tomography (OCT) and Cirrus spectral domain OCT (Carl Zeiss Meditec, Dublin, CA) in normal subjects and glaucoma patients.
Evaluation of diagnostic test or technology.
One hundred thirty eyes from 130 normal subjects and glaucoma patients were analyzed. The subjects were divided into Normal (n=29), Glaucoma Suspect (n=12), Mild Glaucoma (n=41), Moderate Glaucoma (n=18), and Severe Glaucoma (n=30) by visual field criteria.
Peripapillary RNFL thickness was measured with Stratus Fast RNFL and Cirrus 200 x 200 Optic Disc Scan on the same day in one eye of each subject to determine agreement. Two operators used the same instruments for all scans.
Main Outcome Measures
Student paired t-testing, Pearson’s correlation coefficient, and Bland-Altman analysis of RNFL thickness measurements.
The average age of the glaucoma group was significantly older at 68.3±12.3 years versus 55.7±12.1 years. The average RNFL thickness (mean ± SD, in μm) for each severity group with Stratus OCT was 99.4 ± 13.2, 94.5 ± 15.0, 79.0 ± 14.5, 62.7 ± 10.2, and 51.0 ± 8.9, corresponding to normal, suspects, mild, moderate, and severe subjects, respectively. For Cirrus OCT, the corresponding measurements were 92.0 ± 10.8, 88.1 ± 13.5, 73.3 ± 11.8, 60.9 ± 8.3, and 55.3 ± 6.6. All Stratus-Cirrus differences were statistically significant by paired t-testing (p < 0.001) except for the moderate group (p = 0.11). For average RNFL, there was a highly significant linear relationship between Stratus minus Cirrus difference and RNFL thickness as well (p < 0.001). Bland-Altman plots showed that the systematic difference of Stratus measurements are smaller than Cirrus at thinner RNFL values but larger at thicker RNFL measurements.
RNFL thickness measurements between Stratus OCT and Cirrus OCT cannot be directly compared. Clinicians should be aware that measurements are generally higher with Stratus than Cirrus except when the RNFL is very thin as in severe glaucoma. This difference must be taken into account if comparing measurements made with a Stratus instrument to those of a Cirrus instrument.
We used high-resolution spectral-domain optical coherence tomography (SD-OCT) with retinal segmentation to determine how ganglion cell loss relates to history of acute optic neuritis (ON), retinal nerve fiber layer (RNFL) thinning, visual function, and vision-related quality of life (QOL) in multiple sclerosis (MS).
A convenience sample of patients with MS (n = 122; 239 eyes) and disease-free controls (n = 31; 61 eyes). Among MS eyes, 87 had a history of ON before enrollment.
The SD-OCT images were captured using Macular Cube (200×200 or 512×128) and ONH Cube 200×200 protocols. Retinal layer segmentation was performed using algorithms established for glaucoma studies. Thicknesses of the ganglion cell layer/inner plexiform layer (GCL+IPL), RNFL, outer plexiform/inner nuclear layers (OPL+INL), and outer nuclear/photoreceptor layers (ONL+PRL) were measured and compared in MS versus control eyes and MS ON versus non-ON eyes. The relation between changes in macular thickness and visual disability was also examined.
Main Outcome Measures
The OCT measurements of GCL+IPL and RNFL thickness; high contrast visual acuity (VA); low-contrast letter acuity (LCLA) at 2.5% and 1.25% contrast; on the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and 10-Item Neuro-Ophthalmic Supplement composite score.
Macular RNFL and GCL+IPL were significantly decreased in MS versus control eyes (P<0.001 and P = 0.001) and in MS ON versus non-ON eyes (P<0.001 for both measures). Peripapillary RNFL, macular RNFL, GCL+IPL, and the combination of macular RNFL+GCL+IPL were significantly correlated with VA (P≤0.001), 2.5% LCLA (P<0.001), and 1.25% LCLA (P≤0.001). Among OCT measurements, reductions in GCL+IPL (P<0.001), macular RNFL (P = 0.006), and the combination (macular RNFL+GCL+IPL; P<0.001) were most strongly associated with lower (worse) NEI-VFQ-25 and 10-Item Supplement QOL scores; GCL+IPL thinning was significant even accounting for macular RNFL thickness (P = 0.03 for GCL+IPL, P = 0.39 for macular RNFL).
We demonstrated that GCL+IPL thinning is most significantly correlated with both visual function and vision-specific QOL in MS, and may serve as a useful structural marker of disease. Our findings parallel those of magnetic resonance imaging studies that show gray matter disease is a marker of neurologic disability in MS.
To assess the inter-device agreement of peripapillary retinal nerve fiber layer (RNFL) thickness measurements by 2 spectral domain Cirrus HD optical coherence tomography (OCT) devices in healthy Korean subjects.
Eleven eyes of 11 healthy volunteers were enrolled in the present study. Each eye was scanned with the Optic Disc Cube 200 × 200 scan of 2 Cirrus HD OCT devices for peripapillary RNFL thickness calculation. The inter-device agreements of the 2 Cirrus HD OCTs for average, quadrant, and clock-hour RNFL thickness values were determined with Wilcoxon signed rank test, Friedman test, Cronbach's alpha (α), intraclass correlation coefficient (ICC), coefficient of variation (COV), and Bland-Altman plot.
The mean age of the participants was 25.82 ± 3.28 years and all had a 0.00 logarithm of the minimum angle of resolution of best-corrected visual acuity. The signal strengths of scans from the 2 Cirrus HD OCT were not significantly different (p = 0.317). The inter-device agreement of average RNFL thickness was excellent (α, 0.940; ICC, 0.945; COV, 2.45 ± 1.52%). However, the agreement of nasal quadrant RNFL thickness was not very good (α, 0.715; ICC, 0.716; COV, 5.72 ± 4.64%). Additionally, on the Bland-Atman plot, the extent of agreement of the 2 Cirrus HD OCTs for RNFL thickness was variable according to scanned sectors.
The inter-device agreement of 2 spectral domain Cirrus HD OCT devices for peripapillary RNFL thickness measurements was generally excellent but variable according to the scanned area. Thus, physicians should consider this fact before judging a change of RNFL thicknesses if they were measured by different OCT devices.
Inter-device agreement; Optical coherence tomography; Retinal nerve fiber layer thickness
To evaluate correlations between Retinal Nerve Fiber Layer (RNFL) thickness with visual field (VF) sensitivities in eyes with Non-artertic Anterior Ischemic Optic Neuropathy (NAION).
This study was conducted in an academic, institutional setting. One eye from 21 NAION patients and 32 healthy participants were included in this prospective study. Humphrey Visual Field (HVF) sensitivities were obtained from standard achromatic HVF test (24-2 SITA). RNFL was measured with scanning laser polarimetry (GDx-VCC) and optical coherence tomographer (StratusOCT). Correlations were evaluated between RNFL and sensitivities from global, hemifields and regional locations of the VF pertinent to the RNFL distribution. 15 NAION eyes had an inferior altitudinal HVF defects and their global and regional RNFL was compared to that of control eyes. The main outcome measure was correlation between HVF sensitivities and RNFL.
Correlations of global, hemifield and sectorial HVF sensitivities with RNFL were greater when RNFL was measured with StratusOCT than with GDx-VCC, except for nasal and infero-nasal sectors. RNFL thickness was significantly lower in the hemiretinas corresponding to the relative unaffected hemifield in eyes with altitudinal visual field defect compared to controls.
In patients with NAION, RNFL measured by StratusOCT provided better correlation to HVF changes than GDx-VCC did. Both instruments showed decreased RNFL in NAION eyes with altitudinal visual field defects compared to control eyes, demonstrating loss of RNFL even in sectors of the optic disc that corresponded to relatively unaffected hemifield, suggesting greater damaged beyond the extent estimated by visual field methods.
Scanning laser polarimetry (SLP) reveals abnormal retardance of birefringence in locations of the edematous peripapillary retinal nerve fiber layer (RNFL), which appear thickened by optical coherence tomography (OCT), in nonarteritic anterior ischemic optic neuropathy (NAION). We hypothesize initial sector SLP RNFL abnormalities will correlate with long-term regional visual field loss due to ischemic injury.
We prospectively performed automated perimetry, SLP, and high definition OCT (HD-OCT) of the RNFL in 25 eyes with acute NAION. We grouped visual field threshold and RNFL values into Garway-Heath inferior/superior disc sectors and corresponding superior/inferior field regions. We compared sector SLP RNFL thickness with corresponding visual field values at presentation and at >3 months.
At presentation, 12 eyes had superior sector SLP reduction, 11 of which had inferior field loss. Six eyes, all with superior field loss, had inferior sector SLP reduction. No eyes had reduced OCT-derived RNFL acutely. Eyes with abnormal field regions had corresponding SLP sectors thinner (P = 0.003) than for sectors with normal field regions. During the acute phase, the SLP-derived sector correlated with presentation (r = 0.59, P = 0.02) and with >3-month after presentation (r = 0.44, P = 0.02) corresponding superior and inferior field thresholds.
Abnormal RNFL birefringence occurs in sectors corresponding to regional visual field loss during acute NAION when OCT-derived RNFL shows thickening. Since the visual field deficits show no significant recovery, SLP can be an early marker for axonal injury, which may be used to assess recovery potential at RNFL locations with respect to new treatments for acute NAION.
Scanning laser polarimetry measured loss in RNFL birefringence in acute NAION seems to reveal early axonal injury and permanent field loss at presentation.
NAION; retardance; retinal birefringence; OCT; scanning laser polarimetry
To evaluate and compare the diagnostic ability of spectral domain optical coherence tomography (SD-OCT) for detecting localized retinal nerve fiber layer (RNFL) defects in topographic RNFL maps and circumpapillary RNFL (cpRNFL) thickness measurements.
Sixty-four eyes with localized RNFL defects in red-free RNFL photographs and 72 healthy eyes were included. All participants were imaged with SD-OCT. The area and angular width of the localized RNFL defects were measured with ImageJ software on RNFL thickness map, significance map (yellow pixels, <5% level), and red-free RNFL photographs. The sensitivity, specificity, and area under the receiver operating characteristic curves (AUCs) were calculated for cpRNFL thickness, macular inner retina thickness, and RNFL maps (thickness, significance) according to the quantitative measurements and a <5% level of classification to distinguish eyes with localized RNFL defects from healthy eyes.
RNFL thickness map (sensitivity 96.9–98.4%, specificity 86.1–98.6%, and AUCs 0.915–0.992) and significance map (sensitivity 96.9–98.4%, specificity 88.9–95.8%, and AUCs 0.937–0.983) showed superior performance in detecting localized RNFL defects compared with other parameters (P-value 0.001–0.024) except for 36 sector cpRNFL thickness (sensitivity 92.2%, specificity 87.5%, and AUCs 0.898; P-value 0.080–0.545). The sensitivity for detecting RNFL defects was related to the angular width, area, and depth of the RNFL defects in the cpRNFL (4 sector, 12 sector) and macular inner retinal measurements. RNFL thickness and significance maps showed a constant sensitivity regardless of variations in angular width, area, and depth of the RNFL defects.
RNFL thickness and significance maps could be used to distinguish eyes with localized RNFL defects from healthy eyes more effectively than cpRNFL thickness and macular inner retina thickness measurements.
retinal nerve fiber layer defect; optical coherence tomography; diagnostic ability
To investigate the relationship between visual function, measured by standard automated perimetry (SAP), and retinal nerve fiber layer (RNFL) thickness, measured by optical coherence tomography (OCT), in patients with multiple sclerosis (MS).
SAP and RNFL thickness were measured in patients with MS in 28 eyes with the last optic neuritis (ON) ≥6 months prior (ON group) and 33 eyes without ON history (non-ON group). Abnormal overall or quadrant RNFL thickness was defined by measured values below 5% of the norm. A whole visual field or a sector of the field was classified as abnormal by using cluster criteria on total-deviation plots. Agreement between SAP and OCT results in classifying eyes/sectors was presented as a percentage of observed agreement, along with the AC1 statistic, which corrects for chance agreement. Regression analyses were performed relating several SAP parameters and RNFL thickness in the ON group.
ON eyes showed more loss of visual sensitivity (MD, P = 0.02) and more loss of RNFL thickness (P < 0.0001) than did non-ON eyes. SAP and OCT agreed in 86% (AC1 = 0.78) of eyes and 69% (AC1 = 0.38) of sectors in the ON group and 61% (AC1 = 0.33) of eyes and 66% (AC1 = 0.48) of sectors in the non-ON group. Overall RNFL thickness was related to MD (dB) by a simple exponential function (R2 = 0.48), supporting a linear relationship between these measures when both are expressed on linear scales. Absolute Pearson correlation coefficients for overall RNFL thickness and several SAP parameters ranged from 0.51 to 0.69.
Good agreement between SAP and OCT was found in ON eyes but not in non-ON eyes or in individual sectors in either group. The findings in this study provide further support for the utility of combining structural and functional testing in clinical research on patients with MS, as well as in future neuroprotection trials for which the anterior visual pathways in patients with MS and optic neuritis may be used as a model.
To study the relationship between the appearance of the optic nerve and the retinal nerve fiber layer (RNFL) thickness determined by spectral domain optical coherence tomography (OCT).
Records from patients with spectral domain-OCT imaging in a neuro-ophthalmology practice were reviewed. Eyes with glaucoma/glaucoma suspicion, macular/optic nerve edema, pseudophakia, and with refractive errors > 6D were excluded. Optic nerve appearance by slit lamp biomicroscopy was related to the RNFL thickness by spectral domain-OCT and to visual field results.
Ninety-one patients (176 eyes; mean age: 49 ± 15 years) were included. Eighty-three eyes (47%) showed optic nerve pallor; 89 eyes (50.6%) showed RNFL thinning (sectoral or average peripapillary). Average peripapillary RNFL thickness in eyes with pallor (mean ± SD = 76 ± 17 μm) was thinner compared to eyes without pallor (91 ± 14 μm, P < 0.001). Optic nerve pallor predicted RNFL thinning with a sensitivity of 69% and a specificity of 75%. Optic nerve appearance predicted RNFL thinning (with a sensitivity and specificity of 81%) when RNFL had thinned by ∼ 40%. Most patients with pallor had RNFL thinning with (66%) or without (25%) visual field loss; the remainder had normal RNFL and fields (5%) or with visual field abnormalities (4%).
Optic nerve pallor as a predictor of RNFL thinning showed fair sensitivity and specificity, although it is optimally sensitive/specific only when substantial RNFL loss has occurred.
Finding an acceptable relationship between the optic nerve appearance by ophthalmoscopy and spectral domain-OCT RNFL measures will help the clinician's interpretation of the information provided by this technology, which is gaining momentum in neuro-ophthalmic research.
nerve fiber layer; optical coherence tomography; optic nerve pallor
Glaucoma is a progressive disorder and requires serial evaluation in order to monitor disease progression and optimize therapy.
The objective of this study was to determine the correlation between each of cup/disc (C/D) ratio and the disc damage likelihood scale (DDLS) with retinal nerve fiber layer (RNFL) and global indices in Humphrey field analyzer II (HFA II).
Materials and Methods:
A total of 50 patients diagnosed with primary open angle glaucoma were examined to grade DDLS score and C/D ratio. The average (avg) RNFL was obtained using the Fast RNFL protocol on optical coherence tomography (OCT) (4.0.2 Carl Zeiss). HFA II Swedish Interactive Threshold Algorithm Standard 24-2 visual fields were obtained within 1 month of clinical examination. The correlation of C/D ratio with avg RNFL thickness, Mean deviation and Pattern standard deviation was calculated by Pearson correlation coefficient (r). Similar coefficients were obtained for DDLS.
The P value for the difference in the r between C/D ratio with RNFL (−0.628) and DDLS with RNFL (−0.8369) was significant (P < 0.01) when correlation of C/D, DDLS with RNFL was considered.
The DDLS shows stronger correlation with structural changes in OCT than C/D ratio. The disc diameter and rim width increases the value of clinical optic disc examination.
Cup/disc ratio; disc damage likelihood scale; retinal nerve fiber layer thickness; visual field
To report optical coherence tomography (OCT) findings in order to detect subclinical alterations of the afferent visual pathways in spinocerebellar ataxia 3 (SCA-3).
Patients and methods
Nine genetically confirmed patients (18 eyes) were evaluated with a complete ophthalmologic examination including visual acuity, colour vision, visual field test, and retinal nerve fibre layer (RNFL) and macular thickness with OCT Cirrus HD. A neurological examination was performed and the Scale for the Assessment and Rating of Ataxia (SARA score) was determined in all patients.
The mean RNFL thickness was 77.39 microns, standard deviation (SD) was ±5.93. In 15 eyes (83.33%), the mean RNFL thickness was lower than the population average considering age and sex. In 10 cases, there was a reduction of the RNFL thickness in the superior sector, eight in the inferior and four in the nasal. Temporal sector RNFL thickness was preserved in all eyes. RNFL thickness was inversely correlated to SARA score (r=−0.64, P=0.012). The mean macular thickness was 252.61 microns, SD±22.80, being inferior respecting average population in only two eyes (11.11%). In four patients, (eight eyes) OCT studies were performed during a mean follow-up of 14.25 months, and in five eyes (62.50%) there was a mild trend to a RNFL thickness decrease in this period.
A mild and progressive decrease in RNFL thickness can be observed in SCA-3 patients. A negative correlation exists between an anatomic marker (RNFL thickness) and a clinical severity scale (SARA score); thus, RNFL thickness could be considered as a promising biomarker of the disease.
spinocerebellar ataxia 3; optical coherence tomography; retinal nerve fibre layer thickness; macular thickness; SARA score
We determined the time lag between loss of retinal ganglion cell function and retinal nerve fiber layer (RNFL) thickness.
Glaucoma suspects were followed for at least four years. Patients underwent pattern electroretinography (PERG), optical coherence tomography (OCT) of the RNFL, and standard automated perimetry testing at 6-month intervals. Comparisons were made between changes in all testing modalities. To compare PERG and OCT measurements on a normalized scale, we calculated the dynamic range of PERG amplitude and RNFL thickness. The time lag between function and structure was defined as the difference in time-to-criterion loss between PERG amplitude and RNFL thickness.
For PERG (P < 0.001) and RNFL (P = 0.030), there was a statistically significant difference between the slopes corresponding to the lowest baseline PERG amplitude stratum (≤50%) and the reference stratum (>90%). Post hoc comparisons demonstrated highly significant differences between RNFL thicknesses of eyes in the stratum with most severely affected PERG (≤50%) and the two strata with least affected PERG (>70%). Estimates suggested that the PERG amplitude takes 1.9 to 2.5 years to lose 10% of its initial amplitude, whereas the RNFL thickness takes 9.9 to 10.4 years to lose 10% of its initial thickness. Thus, the time lag between PERG amplitude and RNFL thickness to lose 10% of their initial values is on the order of 8 years.
In patients who are glaucoma suspects, PERG signal anticipates an equivalent loss of OCT signal by several years.
Patients suspected of glaucoma had pattern electroretinogram amplitude changes several years before equivalent optical coherence tomography changes.
To evaluate the correlation between automated achromatic perimetry (AAP) and the output of two retinal nerve fiber layer (RNFL) analysers: scanning laser polarimetry (GDx-VCC) and optical coherence tomography (OCT).
Quantitative RNFL measurements with GDx-VCC and Stratus-OCT were obtained in one eye from 52 healthy subjects, 38 ocular hypertensive (OHT) patients and 94 glaucomatous patients. All patients underwent a complete examination, including AAP using the Swedish interactive threshold algorithm (SITA). The relationship between RNFL measurements and SITA visual field global indices were assessed by means of the following methods: analysis of variance, bivariate Pearson's correlation coefficient, multivariate linear regression techniques and nonlinear regression models, and the coefficient of determination (r2) was calculated.
RNFL thickness values were significantly lower in glaucomatous eyes than in healthy and ocular hypertensive eyes for both nerve fiber analysers (P≤0.001), except for the inferior 120° average thickness in GDx-VCC. Linear regression models constructed for GDx-VCC measurements and OCT-derived RNFL thickness with SITA visual field global indices demonstrated that, for the mean deviation, the only predictor in the model was the nerve fiber indicator for GDx-VCC (r2=0.255), and for the pattern standard deviation, the predictors in the model were the nerve fiber indicator for GDx-VCC (r2=0.246) and the maximum thickness in the superior quadrant for Stratus-OCT (r2=0.196). The best curvilinear fit was obtained with the cubic model.
Quantitative measurements of RNFL thickness using either GDx-VCC or OCT correlate moderately with visual field global indices in moderate glaucoma patients. We did not find a correlation between visual field global indices and RNFL thickness in early glaucoma patients. Further study is needed to develop new analytical methods that will increase RNFL analyser's sensitivity in early glaucoma patients.
glaucoma; automated achromatic perimetry; scanning laser polarimetry; optical coherence tomography; glaucoma; perimetría automatizada acromática; polarimetría láser de barrido; tomografía de coherencia óptica
To test a linear model relating the regional loss in retinal nerve fiber (RNFL) thickness to the corresponding regional loss in sensitivity with data from patients with previous anterior ischemic optic neuropathy (AION).
Twenty-four individuals with AION and 20 with normal vision were tested. The time since the AION attack ranged from 5.2 months to more than 20.3 years (median, 2.95 years).
Eyes were tested with standard automated perimetry (SAP) and with optical coherence tomography (OCT), both RNFL thickness scans. The average RNFL thickness of the inferior and superior disc sectors was plotted against the average total deviations (linear units) of the corresponding superior and inferior arcuate field regions, and a linear model was fitted. According to the model, the RNFL thickness R = soT + b, (1), where T is the relative SAP sensitivity loss (on a linear scale; e.g., for −3 dB, T = 0.5), so is the RNFL thickness attributable to axons in the healthy or normal state (T = 1.0), and b is the residual RNFL measured when all sensitivity and axons are lost.
Main Outcome Measures
Optical coherence tomography RNFL thickness and SAP sensitivity.
The data from the AION patients resembled the data from glaucoma patients previously tested and were described by the linear model. For patients with SAP losses of more than −10 dB in the arcuate region, the RNFL thickness provided an estimate of residual RNFL thickness, b. The median value of b (45.5 µm) was similar to the value for patients with glaucoma. It varied among individuals (range, 30.4–63.3 µm), showing a very weak correlation with patient’s age (r = 0.30) and the time since the AION episode (r = 0.26), but an excellent correlation (r2 = 0.94; P<0.01) with the value of so, estimated from the unaffected eyes.
The relationship between a structure (OCT RNFL thickness) and function (SAP sensitivity loss) is the same for patients with AION and glaucoma and can be approximated by a simple linear model. The model may provide a framework for identifying those patients with ganglion cell axons that are malfunctioning but are alive.
To prospectively compare detection of progressive retinal nerve fiber layer thickness (RNFL) atrophy identified using time-domain optical coherence tomography (OCT) with visual field progression using standard automated perimetry (SAP) in glaucoma suspect and preperimetric glaucoma and perimetric glaucoma patients.
Prospective longitudinal clinical trial
Eligible eyes with ≥2 years of follow-up underwent time-domain OCT and SAP every 6 months. The occurrence of visual field progression was defined as the first follow-up visit reaching a significant (p<0.05) negative visual field index (VFI) slope over time. RNFL progression/improvement was defined as a significant negative/positive slope over time. Specificity was defined as the number of eyes with neither progression nor improvement, divided by the number of eyes without progression. Cox proportional hazard ratios (HR) were calculated using univariate and multivariate models with RNFL loss as a time-dependent covariate.
310 glaucoma suspect and preperimetric glaucoma, and 177 perimetric glaucoma eyes were included. Eighty-nine eyes showed visual field progression and 101 eyes showed RNFL progression. The average time to detect visual field progression in those 89 eyes was 35±13 months; and to detect RNFL progression in those 101 eyes was 36±13 months. In multivariate Cox models, average and superior RNFL losses were associated with subsequent VFI loss in the entire cohort (every 10μm loss, HR=1.38,p=0.03; HR=1.20, p=0.01 respectively). Among the entire cohort of 487 eyes, 42 had significant VFI improvement and 55 had significant RNFL improvement (specificity 91.4% and 88.7%, respectively).
Structural progression is associated with functional progression in glaucoma suspect and glaucomatous eyes. Average and superior RNFL thickness may predict subsequent SAP loss.
retinal nerve fiber layer; visual field; glaucoma progression; hazard ratio
Histopathologic studies have reported retinal nerve fiber layer (RNFL) thinning in various neurodegenerative diseases. Attempts to quantify this loss in vivo have relied on time-domain optical coherence tomography (TDOCT), which has low resolution and requires substantial interpolation of data for volume measurements. We hypothesized that the significantly higher resolution of spectral-domain optical coherence tomography (SDOCT) would better detect RNFL changes in patients with multiple sclerosis, and that RNFL thickness differences between eyes with and without optic neuritis might be identified more accurately.
In this retrospective case series, patients with multiple sclerosis were recruited from the Judith Jaffe Multiple Sclerosis Center at Weill Cornell Medical College in New York. Patients with a recent clinical diagnosis of optic neuritis (less than three months) were excluded. Eyes with a history of glaucoma, optic neuropathy (other than multiple sclerosis-related optic neuritis), age-related macular degeneration, or other relevant retinal and/or optic nerve disease were excluded. Both eyes of each patient were imaged with the Heidelberg Spectralis® HRA + OCT. RNFL and macular thickness were measured for each eye using the Heidelberg OCT software. These measurements were compared with validated published normal values, and were modeled as linear functions of duration of disease. The odds of an optic neuritis diagnosis as a function of RNFL and macular thickness were calculated.
Ninety-four eyes were prospectively evaluated using OCT. Ages of patients ranged from 26 to 69 years, with an average age of 39 years. Peripapillary RNFL thinning was demonstrated in multiple sclerosis patients; mean RNFL thickness was 88.5 μm for individuals with multiple sclerosis compared with a reported normal value of 97 μm (P < 0.001). Eyes with a history of optic neuritis had more thinning compared with those without optic neuritis (83.0 μm versus 90.5 μm, respectively, P = 0.02). No significant differences were observed in macular thickness measurements between eyes with and without optic neuritis, nor were macular thickness measurements significantly different from normal values. As a function of multiple sclerosis duration and controlling for age, RNFL thickness was decreased in patients with a duration of multiple sclerosis greater than five years compared with those with a duration less than or equal to one year (P = 0.008).
Patients with a history of multiple sclerosis had RNFL thinning that was detectable on SDOCT. Decreasing RNFL thickness in eyes with optic neuritis was found, and the odds of having optic neuritis were increased significantly with decreasing RNFL thickness. Average RNFL thinning with increasing duration of disease was an excellent predictor of a reported history of optic neuritis. SDOCT retinal imaging may represent a high-resolution, objective, noninvasive, and easily quantifiable in vivo biomarker of the presence of optic neuritis and severity of multiple sclerosis.
multiple sclerosis; spectral-domain optical coherence tomography; optical coherence tomography; nerve fiber layer; nerve fiber layer thickness; optic neuritis
Optical coherence tomography (OCT) shows retinal nerve fiber layer (RNFL) thickening in optic nerve head (ONH) swelling, but does not provide information on acute axonal disruption. It was hypothesized that scanning laser polarimetry (SLP) compared with OCT might reveal the status of axon integrity and visual prognosis in acute RNFL swelling.
Threshold perimetry, OCT, and SLP were used to prospectively study eyes with papilledema (24), optic neuritis (14), nonarteritic anterior ischemic optic neuropathy (NAION) (21), and ONH swelling (average RNFL value by OCT was above the 95th percentile of controls at presentation). Regional RNFL was judged reduced if the quadrant measurement was below the fifth percentile of controls.
At presentation, average RNFL by OCT was similar for eyes with papilledema and NAION (P = 0.97), and reduced for optic neuritis. Average RNFL by SLP was slightly increased for papilledema and optic neuritis, and reduced for NAION (P = 0.02) eyes. The RNFL by SLP was reduced in at least one quadrant in 1 eye with papilledema, 1 eye with optic neuritis, and in 13 eyes with NAION. In NAION eyes, quadrants with reduced SLP had corresponding visual field loss that did not recover. By one month, eyes with NAION showed RNFL thinning by OCT (7/17 eyes) and by SLP (14/16 eyes) in contrast to optic neuritis (by OCT, 0/12, P = 0.006; and by SLP, 1/12, P = 0.0004).
OCT and SLP revealed different aspects of RNFL changes associated with ONH swelling. OCT revealed thickening due to edema. SLP revealed a decrease in retardance in eyes with axonal injury associated with visual field loss, which is unlikely to recover.
SLP seems to be predictive of regions of permanent axon dysfunction and visual field loss in eyes with optic disc edema.
To determine the effects of age on global and sectoral peripapillary retinal nerve fiber layer (RNFL), macular thicknesses and optic nerve head (ONH) parameters in healthy subjects using optical coherence tomography (OCT).
Retrospective, cross-sectional observational study.
226 eyes from 124 healthy subjects were included.
Healthy subjects were scanned using the Fast RNFL, Fast Macula, and Fast ONH scan patterns on a Stratus OCT. All global and sectoral RNFL and macular parameters and global ONH parameters were modeled in terms of age using linear mixed effects models. Normalized slopes were also calculated by dividing the slopes by the mean value of the OCT parameter for inter-parameter comparison.
Main Outcome Measures
Slope of each OCT parameter across age.
All global and sectoral RNFL thickness parameters statistically significantly decreased with increasing age, except for the temporal quadrant and clock hours 8-10, which were not statistically different from a slope of zero. Highest absolute slopes were in the inferior and superior quadrant RNFL and clock hour 1 (superior nasal). Normalized slopes showed similar rate in all sectors except for the temporal clock hours (8-10). All macular thickness parameters statistically significantly decreased with increasing age, except for the central fovea sector, which had a slight positive slope that was not statistically significant. The nasal outer sector had the greatest absolute slope. Normalized macular slope in the outer ring was similar to the normalized slopes in the RNFL. Normalized inner ring had shallower slope than the outer ring with similar rate in all quadrants. Disc area remained nearly constant across the ages, but cup area increased and rim area decreased with age, both of which were statistically significant.
Global and regional changes due to the effects of age on RNFL, macula and ONH OCT measurements should be considered when assessing eyes over time.
To establish and validate a formula to predict spectral domain (SD)-optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) thickness from time domain (TD)-OCT RNFL measurements and other factors.
SD-OCT and TD-OCT scans were obtained on the same day from healthy participants and patients with glaucoma. Univariate and multivariate linear regression relationships were analyzed to convert average Stratus TD-OCT measurements to average Cirrus SD-OCT measurements. Additional baseline characteristics included age, sex, intraocular pressure, central corneal thickness, spherical equivalent, anterior chamber depth, optic disc area, visual field (VF) mean deviation, and pattern standard deviation. The formula was generated using a training set of 220 patients and then evaluated on a validation dataset of 105 patients.
The training set included 71 healthy participants and 149 patients with glaucoma. The validation set included 27 healthy participants and 78 patients with glaucoma. Univariate analysis determined that TD-OCT RNFL thickness, age, optic disc area, VF mean deviation, and pattern standard deviation were significantly associated with SD-OCT RNFL thickness. Multivariate regression analysis using available variables yielded the following equation: SD-OCT RNFL = 0.746 × TD-OCT RNFL + 17.104 (determination coefficient [R2] = 0.879). In the validation sample, the multiple regression model explained 85.6% of the variance in the SD-OCT RNFL thickness.
The proposed formula based on TD-OCT RNFL thickness may be useful in predicting SD-OCT RNFL thickness. Other factors associated with SD-OCT RNFL thickness, such as age, disc area, and mean deviation, did not contribute to the accuracy of the final equation.
Glaucoma; Retinal nerve fiber layer; Spectral domain optical coherence tomography; Time domain optical coherence tomography
To investigate peripapillary retinal nerve fiber layer (RNFL) thickness of healthy Chinese individuals from northwestern Shanghai using Cirrus HD-OCT (Carl Zeiss Meditec, Inc. Dublin, CA, USA).
The peripapillary RNFL thickness of 720 eyes from 360 healthy Chinese participants were measured using the Optic Disc Cube 200×200 protocol. Each eye was scanned 3 times. Global and each quadrant's RNFL thickness around the optic nerve were compared between genders, and interocular differences were analyzed. The correlation between global RNFL thickness and age were also assessed in this study.
The mean global, superior, nasal, inferior and temporal RNFL thickness of all the eyes were 96.04±7.40 µm, 118.36±13.52 µm, 67.63±8.60 µm, 125.17±13.48 µm, 72.49±10.70 µm, respectively. When analyzing between genders, the mean nasal RNFL thickness of male and female were 68.29±8.44 µm and 66.97±8.70 µm, with statistically significant difference (P=0.038), while the data of global, superior, inferior and temporal quadrant showed no significant difference (all P>0.05). When analyzing interocular differences, the mean RNFL thickness of all the right eyes and all the left eyes were 116.46±13.17 µm and 120.27±13.61 µm in superior quadrant (P<0.001); 68.74±8.80 µm and 66.52±8.25 µm in nasal quadrant (P<0.001); 73.16±10.95 and 71.83±10.41 in temporal quadrant (P<0.001), all having statistically significant differences. There were no statistically significant interocular differences of global and inferior RNFL thickness (both P>0.05). There was a significantly negative correlation (r=-0.618, P<0.001) between the mean global RNFL thickness and the age.
In healthy Chinese from northwestern Shanghai, there were no significant differences detected interocular difference and between genders in the mean global RNFL thickness. Nevertheless, significant difference existed in the nasal quadrant between genders, and interocular differences existed in the superior, nasal and temporal quadrants. The RNFL thickness appeared to gradually decrease with age.
retinal nerve fiber layer; optical coherence tomography; Chinese
To evaluate the use of optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) thickness and visual field (VF) measurements in detecting disease progression in patients with early glaucoma.
Over a 3-year period, this study examined 60 eyes of 39 glaucoma patients whose total deviation in the superior or inferior hemifield was more than -6 dB. All eyes underwent at least four serial RNFL measurements performed by Cirrus OCT, with the first and last measurements separated by at least three years. On the same day as the RNFL imaging, VF testing was also performed by using the Swedish Interactive Threshold Algorithm Standard 30–2 program of the Humphrey Field Analyzer. Serial RNFL thicknesses and VF progression were assessed using the Guided Progression Analysis (GPA) software program. RNFL thickness progression and VF progression were evaluated by the event analysis.
The mean observation period was 57.6 ± 10.0 months, and during this time, a total of 366 OCT and 366 VF measurements were performed. Using only OCT, progression was found in 2 eyes, while progression was found in 1 eye when only using VF GPA. When combined measurement findings were used, the analysis found progression in 8 eyes.
When mild VF defect is present, OCT RNFL thickness measurements can be helpful in discerning glaucoma progression.
Optical coherence tomography; Visual field; Retinal nerve fiber layer; Glaucoma progression
An assessment of the retinal nerve fiber layer (RNFL) provides important information on the health of the optic nerve. There are several non-invasive technologies, including spectral domain optical coherence tomography (SD-OCT), that can be used for in vivo imaging and quantification of the RNFL, but often there is disagreement in RNFL thickness between clinical instruments. The purpose of this study was to investigate the influence of scan centration, ocular magnification and segmentation on the degree of agreement of RNFL thickness measures by two SD-OCT instruments.
RNFL scans were acquired from forty-five normal eyes using two commercially available SD-OCT systems. Agreement between RNFL thickness measures was determined using each instrument's algorithm for segmentation and a custom algorithm for segmentation. The custom algorithm included ocular biometry measures to compute the transverse scaling for each eye. Major retinal vessels were identified and removed from RNFL measures in 1:1 scaled images. Transverse scaling was also used to compute the RNFL area for each scan.
Instrument derived global RNFL thickness measured from the two instruments correlated well (R2 = 0.70, p<0.01), but with significant differences between instruments (mean of 6.7 µm; 95% limits of agreement of 16.0 µm to −2.5 µm, ICC = 0.62). For recentered scans with custom RNFL segmentation, the mean difference was reduced to 0.1 µm (95% limits of agreement 6.1 µm to −5.8 µm, ICC = 0.92). Global RNFL thickness was related to axial length (R2 = 0.24, p<0.01), while global RNFL area measures were not (R2 = 0.004, p = 0.66). Major retinal vasculature accounted for 11.3±1.6% (Cirrus) or 11.8±1.4% (Spectralis) of the RNFL thickness/area measures.
Sources of disagreement in RNFL measures between SD-OCT instruments can be attributed to the location of the scan path and differences in their retinal layer segmentation algorithms. In normal eyes, the major retinal vasculature accounts for a significant percentage of the RNFL and is similar between instruments. With incorporation of an individual's ocular biometry, RNFL area measures are independent of axial length, with either instrument.
retinal nerve fiber layer; spectral domain optical coherence tomography; ocular biometry
To evaluate spectral-domain (SD) optical coherence tomography (OCT) reproducibility and assess the agreement between SD-OCT and Time-Domain (TD) OCT retinal nerve fibre layer (RNFL) measurements.
Three Cirrus-SD-OCT scans and one Stratus-TD-OCT scan were obtained from Diagnostic Innovations in Glaucoma Study (DIGS) healthy participants and glaucoma patients on the same day. Repeatability was evaluated using Sw (within-subject standard deviation), CV (coefficient of variation) and ICC (intraclass correlation coefficient). Agreement was assessed using correlation and Bland–Altman plots.
16 healthy participants (32 eyes) and 39 patients (78 eyes) were included. SD-OCT reproducibility was excellent in both groups. The CV and ICC for Average RNFL thickness were 1.5% and 0.96, respectively, in healthy eyes and 1.6% and 0.98, respectively, in patient eyes. Correlations between RNFL parameters were strong, particularly for average RNFL thickness (R2 = 0.92 in patient eyes). Bland–Altman plots showed good agreement between instruments, with better agreement for average RNFL thickness than for sectoral RNFL parameters (for example, at 90 μm average RNFL thickness, 95% limits of agreement were −13.1 to 0.9 for healthy eyes and −16.2 to −0.3 μm for patient eyes).
SD-OCT measurements were highly repeatable in healthy and patient eyes. Although the agreement between instruments was good, TD-OCT provided thicker RNFL measurements than SD-OCT. Measurements with these instruments should not be considered interchangeable.