To review the ability of current imaging technologies to provide estimates of rates of structural change in glaucoma patients.
Patients and methods
Review of literature.
Imaging technologies, such as confocal scanning laser ophthalmoscopy (CSLO), scanning laser polarimetry (SLP), and optical coherence tomography (OCT), provide quantifiable and reproducible measurements of the optic disc and parapapillary retinal nerve fibre layer (RNFL). Rates of change as quantified by the rim area (RA) (for CSLO) and RNFL thickness (for SLP and OCT) are related to glaucoma progression as detected by conventional methods (eg, visual fields and optic disc photography). Evidence shows that rates of RNFL and RA loss are significantly faster in progressing compared with non-progressing glaucoma patients.
Measurements of rates of optic disc and RNFL change are becoming increasingly precise and individualized. Currently available imaging technologies have the ability to detect and quantify progression in glaucoma, and their measurements may be suitable end points in glaucoma clinical trials.
glaucoma; rate of change; scanning laser polarimetry; confocal scanning laser ophthalmoscopy; optical coherence tomography; imaging technology
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.
To investigate the correlation between retinal nerve fiber layer (RNFL) thickness determined by optical coherence tomography (OCT) and visual field (VF) parameters in patients with optic atrophy.
This study was performed on 35 eyes of 28 patients with optic atrophy. RNFL thickness was measured by OCT (Carl Zeiss, Jena, Germany) and automated perimetry was performed using the Humphrey Field Analyzer (Carl Zeiss, Jena, Germany). The correlation between RNFL thickness and VF parameters was evaluated.
Mean global RNFL thickness was 44.9±27.5 μm which was significantly correlated with mean deviation score on automated perimetry (r=0.493, P=0.003); however, no significant correlation was observed between visual field pattern standard deviation and the corresponding quadrantic RNFL thickness. In a similar manner, no significant association was found between visual acuity and RNLF thickness.
Mean global RNFL thickness as determined by OCT seems to be correlated with VF defect depth as represented by the mean deviation score on Humphrey VF testing. OCT may be used as an objective diagnostic tool in the evaluation of patients with optic atrophy.
To determine the discriminating ability of retinal nerve fiber layer (RNFL) thickness measured with spectral-domain optical coherence tomography (SD-OCT) in different stages of glaucoma.
Patients and methods
Thirty normal, 150 glaucomatous eyes were included. Glaucomatous eyes were graded into early, moderate and severe stages according to one of the global indices called visual field index (VFI). Complete ophthalmic examination, white on white perimetry and SD-OCT were done for all patients. RNFL thickness of quadrants and average thickness were recorded. Area under receiver operating characteristic curves (AUCs) were used to assess the performance of OCT parameters.
Average, inferior and superior RNFL thickness were the best parameters to discriminate normal from early glaucoma (AUC: 0.91–86), early from moderate (AUC: 0.77–0.70) and moderate from severe (AUC: 0.85–83). Average RNFL loss was 18% in early glaucoma, 28% in moderate glaucoma and 41% in severe glaucoma. Early damage tends to be focal and in the lower quadrant. A significant correlation was detected between mean VFI and mean RNFL loss. Glaucoma was restaged according to average RNFL loss into early: ⩾97.5 μ, moderate: <97.5–72.5 μ and severe: <72.5 μ.
RNFL thickness measured with SD-OCT could discriminate the three stages of glaucoma. RNFL loss can be correlated to visual field loss. Future OCT-based staging of glaucoma, adjunctive to perimetry is possible.
Discrimination; Glaucoma; Optical coherence tomography; Perimetry; Stages
To investigate the measures of validity for selective or population screening of the time-domain Stratus and the spectral-domain Cirrus Optical Coherence Tomography (OCT) imaging techniques in a population-based sample and in clinical glaucoma patients at different stages of glaucoma.
Patients and methods
A random sample of 307 subjects living in two rural areas in southern Sweden, and a random sample of 394 clinical glaucoma patients were selected. A large battery of examinations, including Stratus and Cirrus OCT was performed. OCT retinal nerve fibre layer (RNFL) thickness analyses for average thickness, quadrant and clock-hour sectors were compared with normative significance limits available in the instruments.
The population-based sample included 129 healthy and nine glaucoma subjects, and the sample of clinical glaucoma patients included 138 patients. Specificity and positive predictive values were generally better with Stratus than for Cirrus, and sensitivity was generally better with Cirrus. With the average RNFL thickness parameter, Stratus reached 100% specificity and a positive predictive value of 100% and 68% sensitivity in the whole group of the clinical glaucoma patients, but sensitivity was only 28% among the earliest stage glaucoma patients. Sensitivity increased considerably when relying on the quadrant sector parameter, while specificity decreased only marginally.
Stratus, with high specificity and positive predictive values, seemed to be best of choice for screening purposes, while Cirrus, with high sensitivity, was the better choice for early detection.
diagnosis; glaucoma; optical coherence tomography; retinal nerve fibre layer thickness; screening
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.
compared retinal nerve fiber layer (RNFL) bias and imprecision among three spectral-domain optical coherence tomographs (SD-OCT).
A total of 152 eyes of 83 subjects (96 healthy and 56 glaucomatous eyes) underwent peripapillary RNFL imaging using at least 2 of the following 3 SD-OCT devices on the same day: Cirrus HD-OCT (optic nerve head [ONH]) cube 200 × 200 protocol), RTVue-100 (ONH protocol [12 radial lines and 13 concentric circles]), and 3D OCT-1000 (3D Scan 256 × 256 protocol). Calibration equations, bias and imprecision of RNFL measurements were calculated using structural equation models.
The calibration equations for healthy and glaucoma RNFL thickness measurements among the 3 devices were: Cirrus = 2.136 + 0.831*RTVue; Cirrus = −15.521 + 1.056*3D OCT-1000; RTVue = −21.257 + 1.271*3D OCT-1000. Using Cirrus bias as an arbitrary reference, RTVue bias was 1.20 (95% CI 1.09–1.32, P < 0.05) times larger and 3D OCT-1000 was 0.95 (0.87–1.03, P > 0.05) times smaller. Relative to 3D OCT-1000, the RTVue bias was 1.27 (1.13–1.42, P < 0.05). RTVue imprecision (healthy eyes 7.83, 95% CI 6.43–9.58; glaucoma cases 5.71, 4.19–7.64) was statistically significantly higher than both Cirrus (healthy eyes 3.23, 2.11–4.31; glaucoma cases 3.53, 0.69–5.24) and 3D OCT-1000 (healthy eyes 4.07, 3.11–5.35; glaucoma cases 5.33, 3.77–7.67) in healthy eyes. The imprecision also was significantly higher for RTVue measurements in healthy compared to glaucomatous eyes. None of the other comparisons was statistically significant.
RTVue-100 showed higher imprecision (or higher measurement variability) than Cirrus HD-OCT and 3D OCT-1000 RNFL measurements. Three-dimensional cube scanning with post-hoc data sampling may be a factor reducing imprecision.
RTVue-100 showed worse imprecision (higher measurement variability) than Cirrus HD-OCT and 3D OCT-1000 retinal nerve fiber layer measurements. The results might be related to the use of raster scanning by the later devices, while RTVue uses a combination of radial and concentric scanning pattern.
Three patients with progressive visual loss, chronic alcoholism and tabagism were submitted to a complete neuro-ophthalmic examination and to retinal nerve fiber layer (RNFL) measurements using optical coherence tomography (OCT) scanning. Two patients showed marked RNFL loss in the temporal sector of the optic disc. However, a third patient presented RNFL measurements within or above normal limits, based on the Stratus-OCT normative database. Such findings may be due to possible RNFL edema similar to the one that may occur in the acute phase of toxic optic neuropathies. Stratus-OCT was able to detect RNFL loss in the papillomacular bundle of patients with tobacco-alcohol-induced toxic optic neuropathy. However, interpretation must be careful when OCT does not show abnormality in order to prevent diagnostic confusion, since overestimation of RNFL thickness measurements is possible in such cases.
Optical coherence tomography; papillomacular bundle; retinal nerve fiber layer thickness; tobacco-alcohol amblyopia; tobacco-alcohol optic neuropathy
To investigate the relationship between retinal nerve fiber layer (RNFL) thickness and retinal pigment epithelium alterations in patients with advanced glaucomatous visual field defects.
A consecutive, prospective series of 82 study eyes with primary open-angle glaucoma and advanced glaucomatous visual field defects were included in this study. All study participants underwent a full ophthalmic examination followed by visual field testing with standard automated perimetry as well as spectral-domain optical coherence tomography (SD-OCT) for peripapillary RNFL thickness and Optos wide-field fundus autofluorescence (FAF) images. A pattern grid with corresponding locations between functional visual field sectors and structural peripapillary RNFL thickness was aligned to the FAF images at corresponding location. Mean FAF intensity (range: 0 = black and 255 = white) of each evaluated sector (superotemporal, temporal, inferotemporal, inferonasal, nasal, superonasal) was correlated with the corresponding peripapillary RNFL thickness obtained with SD-OCT.
Correlation analyses between sectoral RNFL thickness and standardized FAF intensity in the corresponding topographic retina segments revealed partly significant correlations with correlation coefficients ranging between 0.004 and 0.376 and were statistically significant in the temporal inferior central field (r = 0.324, P = 0.036) and the nasal field (r = 0.376, P = 0.014).
Retinal pigment epithelium abnormalities correlate with corresponding peripapillary RNFL damage, especially in the temporal inferior sector of patients with advanced glaucomatous visual field defects. A further evaluation of FAF as a potential predictive parameter for glaucomatous damage is necessary.
glaucoma; fundus autofluorescence; FAF; retinal nerve fiber layer; RNFL; optical coherence tomography; OCT; imaging
To determine if there were differences in the structure-function relationship between early and advanced glaucoma, and study the association between thicknesses of discrete macular cell layers, the thicknesses of the retinal nerve fibre layer and visual field sensitivity.
Seventy-one eyes of 50 subjects (28 glaucoma patients and 22 normal control subjects) were included. Thicknesses of mRNFL (macular retinal nerve fibre layer), mIRL (macular inner retinal layer) and mORL (macular outer retinal layer) were measured from StratusOCT macular scans, using our previously-published segmentation algorithm. Visual sensitivity loss was determined by mean deviation (MD) using Humphrey Visual Field Analyzer. The mean thickness for each layer from the normal control subjects, early and advanced glaucoma groups was compared. Additionally, a mixed model analysis was used to explore the relationship between structure-function, allowing for possible interaction with glaucoma stage.
The mean mRNFL thickness in early and advanced glaucoma patients was significantly less than measurements in normal subjects (p<0.01). The mean mIRL thickness in advanced glaucoma was significantly less than normal subjects (p=0.04). The mean mORL thickness in early and advanced glaucoma was not statistically significant different from that of normal subjects (p>0.8). There was no statistically significant difference in macular structure-function relationship between the two glaucoma groups (p>0.05). Mean mIRL thickness was significantly associated with MD (p=0.04).
There was no significant difference in macular structure-function relationship between early and advanced glaucoma groups. Combined data from both glaucoma groups indicated that mIRL thickness was associated with visual sensitivity loss.
AIM—To quantitatively evaluate retinal nerve fibre layer (RNFL) difference in areas of apparently normal appearing visual field in eyes with high tension glaucoma (HTG) and hemifield defects using scanning laser polarimetry.
METHODS—40 eyes from 40 patients with HTG with superior or inferior hemifield defects based on the Humphrey field analyser (HFA) underwent RNFL thickness measurements. 20 normal eyes from 20 subjects matched in age and refractive error were selected as a control group. The RNFL thickness was measured with a scanning laser polarimeter. Mean RNFL thickness was evaluated in four quadrants (superior, inferior, nasal, and temporal). A superior or inferior quadrant in the defined ring of scanning laser polarimetry corresponds to inferior or superior hemifield in HFA.
RESULTS—The mean RNFL thickness in the unaffected quadrant (the quadrant corresponding to the hemifield with apparently normal visual field based on HFA) of the HTG group was significantly thinner than the average RNFL thickness of the corresponding quadrant of the control eyes. The RNFL thickness of the unaffected quadrant in the eyes with HTG was reduced and statistically similar to that of the affected quadrant. Symmetry, calculated as the ratio of superior to inferior RNFL thickness, showed no statistical difference between the study and control group.
CONCLUSION—Changes in RNFL are present in the apparently normal hemifield in the eyes with HTG. The thickness of the RNFL is reduced symmetrically in both superior and inferior quadrants based on the GDx parameters.
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 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 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.
Glaucoma is a group of diseases characterised by retinal ganglion cell dysfunction and death. Detection of glaucoma and its progression are based on identification of abnormalities or changes in the optic nerve head (ONH) or the retinal nerve fibre layer (RNFL), either functional or structural. This review will focus on the identification of structural abnormalities in the RNFL associated with glaucoma.
A variety of new techniques have been created and developed to move beyond photography, which generally requires subjective interpretation, to quantitative retinal imaging to measure RNFL loss. Scanning laser polarimetry uses polarised light to measure the RNFL birefringence to estimate tissue thickness. Optical coherence tomography (OCT) uses low-coherence light to create high-resolution tomographic images of the retina from backscattered light in order to measure the tissue thickness of the retinal layers and intraretinal structures. Segmentation algorithms are used to measure the thickness of the retinal nerve fibre layer directly from the OCT images. In addition to these clinically available technologies, new techniques are in the research stages. Polarisation-sensitive OCT has been developed that combines the strengths of scanning laser polarimetry with those of OCT. Ultra-fast techniques for OCT have been created for research devices. The continued utilisation of imaging devices into the clinic is refining glaucoma assessment. In the past 20 years glaucoma has gone from a disease diagnosed and followed using highly subjective techniques to one measured quantitatively and increasingly objectively.
To assess the impact of axial length on the age-related peripapillary retinal nerve fiber layer (RNFL) thinning.
This cross-sectional observational comparative case series included 172 eyes from 172 healthy Korean subjects. Peripapillary RNFL thickness was measured using an Optic Disc Cube 200 × 200 scan of spectral domain Cirrus HD OCT and the axial length was measured using IOL Master Advanced Technology. In age groups based on decade, the normal ranges of peripapillary RNFL thickness for average, quadrant, and clock-hour sectors were determined with 95% confidence intervals. After dividing the eyes into two groups according to axial length (cut-off, 24.50 mm), the degrees of age-related RNFL thinning were compared.
Among the eyes included in the study, 53 (30.81%) were considered to be long eyes (axial length, 25.04 ± 0.48 µm) and 119 (69.19%) were short-to-normal length eyes (axial length, 23.57 ± 0.60 µm). The decrease in average RNFL thickness with age was less in long eyes (negative slope, -0.12 µm/yr) than in short-to-normal length eyes (negative slope, -0.32 µm/yr) (p < 0.001).
Age-related thinning of peripapillary RNFL thickness is attenuated in long eyes compared to short-to-normal length eyes.
Axial length; Glaucoma; Optical coherence tomography; Retinal ganglion cell
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 evaluate the structure-function relationships between retinal sensitivity measured by Humphrey visual field analyzer (HVFA) and the retinal nerve fiber layer (RNFL) thickness measured by scanning laser polarimetry (SLP) with variable corneal compensation (VCC) and enhanced corneal compensation (ECC) in glaucomatous and healthy eyes.
Fifty-three eyes with an atypical birefringence pattern (ABP) based on SLP-VCC (28 glaucomatous eyes and 25 normal healthy eyes) were enrolled in this cross-sectional study. RNFL thickness was measured by both VCC and ECC techniques, and the visual field was examined by HVFA with 24-2 full-threshold program. The relationships between RNFL measurements in superior and inferior sectors and corresponding retinal mean sensitivity were sought globally and regionally with linear regression analysis in each group. Coefficients of the determination were calculated and compared between VCC and ECC techniques.
In eyes with ABP, R2 values for the association between SLP parameters and retinal sensitivity were 0.06-0.16 with VCC, whereas they were 0.21-0.48 with ECC. The association of RNFL thickness with retinal sensitivity was significantly better with ECC than with VCC in 5 out of 8 regression models between SLP parameters and HVF parameters (P<0.05).
The strength of the structure-function association was higher with ECC than with VCC in eyes with ABP, which suggests that the ECC algorithm is a better approach for evaluating the structure-function relationship in eyes with ABP.
GDx-ECC; GDx-VCC; Structure-function relationship; Scanning laser polarimetry
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
In this study, a decrease in RNFL reflectance was found near the ONH in glaucomatous eyes. The change preceded thinning of the RNFL, suggesting that a decrease in RNFL reflectance near the ONH is an early sign of glaucomatous damage.
Glaucoma damages the retinal never fiber layer (RNFL). RNFL thickness, measured with optical coherence tomography (OCT), is often used in clinical assessment of the damage. In this study the relation between the RNFL reflectance and thickness at early stages of glaucoma was investigated.
A rat model of glaucoma was used that involved laser photocoagulation of the trabecular meshwork. The reflectance of the RNFL in an isolated retina was measured, followed by immunohistochemical staining of the axonal cytoskeleton. RNFL thickness was measured by confocal fluorescence imaging. RNFL reflectance was calculated for bundle areas located at radii of 0.22, 0.33, and 0.44 mm from the optic nerve head (ONH) center. Linear regression was used to study the relation between reflectance and thickness. For glaucomatous eyes, only those bundles with no apparent structural damage were used.
Bundles in 11 control retinas and 10 treated retinas were examined. Bundle thickness of both groups at each radius was similar (P = 0.89). The reflectance of the bundles at radii of 0.33 and 0.44 mm was found to be similar in both control and treated retinas (P > 0.5). However, the reflectance of the bundles at the 0.22-mm radius decreased significantly in the treated group (P = 0.005).
Elevation of intraocular pressure causes decrease in RNFL reflectance for bundles near the ONH. Change in RNFL reflectance precedes thinning of the RNFL. The results suggest that a decrease in RNFL reflectance near the ONH is an early sign of glaucomatous damage.
To evaluate the effect of axial length on the variability of retinal nerve fiber layer (RNFL) thickness measurements using the Stratus optical coherence tomography (OCT) in normal and glaucomatous eyes.
We measured the RNFL thickness in 474 subjects using the Stratus OCT twice during the same day. Axial length was measured with the IOLMaster, and refractive error was the absolute value of the spherical equivalent measured with an auto ref-keratometer. Standard deviation in overall mean RNFL thickness was used as the dependent variable to identify significant correlations.
Long axial length affected the variability in the RNFL thickness value by stratus OCT at the temporal quadrant (p = 0.006) and clock-hour sector 9 (p = 0.001). Refractive error also affected the variability of the RNFL thickness value by stratus OCT at the temporal quadrant (p = 0.025) and clock-hour sector 9 (p = 0.024).
It is clinically significant that longer axial length demonstrates greater variability in temporal area as detected by OCT, a measurement which correlates with the preferably damaged position in the myopic glaucoma eye.
Axial eye length; Glaucoma; Optical coherence tomography; Variability
To present full ophthalmologic examination and retinal nerve fiber layer (RNFL) photographs of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) patients showing significant increases in RNFL thickness compared to healthy subjects, but without myelinated retinal fibers.
The study design was observational case series. Ten eyes of five patients with molecular confirmation of ARSACS underwent a full ophthalmologic examination that included clinical history, visual acuity, biomicroscopy of the anterior segment, gonioscopy, Goldmann applanation tonometry, central corneal ultrasonic pachymetry, ophthalmoscopy of the posterior segment, standard automatic perimetry (Humphrey field), simultaneous stereophotographs of the optic disc after mydriasis, a series of five red-free digital fundus photographs for RNFL evaluation, topographic analysis of the optic disc using the Heidelberg retina tomography, and measurement of peripapillary RNFL thickness with Cirrus optical coherence tomography.
All patients showed abnormal visual fields, normal optic discs with a mild to strikingly increased visibility of RNFL in color stereophotographs, normal Heidelberg tomography, and moderate to markedly increased RNFL thickness in Cirrus tomography (average thickness ranging from 119 μm to 220 μm).
We found evidence of RNFL hypertrophy in ARSACS patients that may have been interpreted as hypermyelinated retinal fibers in previous reports. A revision of ARSACS diagnostic criteria, particularly with regard to retinal alterations, is necessary.
Aim: To investigate the correlation between retinal nerve fibre layer (RNFL) thickness and optic nerve head (ONH) size in normal white subjects by means of optical coherence tomography (OCT).
Methods: 54 eyes of 54 healthy subjects aged between 15 and 54 underwent peripapillary RNFL thickness measurement by a series of three circular scans with a 3.4 mm diameter (Stratus OCT, RNFL Thickness 3.4 acquisition protocol). ONH analysis was performed by means of six radial scans centred on the optic disc (Stratus OCT, Fast Optic Disc acquisition protocol). The mean RNFL values were correlated with the data obtained by ONH analysis.
Results: The superior, nasal, and inferior quadrant RNFL thickness showed a significant correlation with the optic disc area (R = 0.3822, p = 0.0043), (R = 0.3024, p = 0.026), (R = 0.4048, p = 0.0024) and the horizontal disc diameter (R = 0.2971, p = 0.0291), (R = 0.2752, p = 0.044), (R = 0.3970, p = 0.003). The superior and inferior quadrant RNFL thickness was also positively correlated with the vertical disc diameter (R = 0.3774, p = 0.0049), (R = 0.2793, p = 0.0408). A significant correlation was observed between the 360° average RNFL thickness and the optic disc area and the vertical and horizontal disc diameters of the ONH (R = 0.4985, p = 0.0001), (R = 0.4454, p = 0.0007), (R = 0.4301, p = 0.0012).
Conclusions: RNFL thickness measurements obtained by Stratus OCT increased significantly with an increase in optic disc size. It is not clear if eyes with large ONHs show a thicker RNFL as a result of an increased amount of nerve fibres or to the shorter distance between the circular scan and the optic disc edge.
optical coherence tomography; optic disc; retinal nerve fibre layer
We describe a patient with ocular hypertension and non-glaucomatous retinal nerve fiber layer (RNFL) atrophy associated with an ocular toxoplasmosis retinal lesion.
Patient and Method
Single case report
An RNFL defect was identified adjacent to a circumscribed pigmented chorioretinal lesion superior to the macular region. The optic disc showed a prominent central cup without focal neural rim atrophy. Red-free photography and RNFL imaging using optical coherence tomography and scanning laser polarimetry showed corresponding focal RNFL atrophy. The toxoplasmosis lesion was characterized by an apparent full thickness disruption in retinal architecture, including the retinal ganglion cell layer, using spectral-domain OCT.
Non-glaucomatous retinal lesions may simulate glaucomatous RNFL atrophy and visual field loss, particularly when focal damage to the retinal ganglion cells occurs. Careful inspection of the retina and, optic disc with attention to the integrity of the neural rim, and analysis of the pattern of RNFL loss in proximity to a retinal lesion, may enable the clinician to differentiate glaucomatous and non-glaucomatous pathogenic mechanisms.
To evaluate the effects of various factors on the variability of retinal nerve fiber layer (RNFL) thickness measurements using the Stratus optical coherence tomography (OCT) in normal and glaucomatous eyes.
Four hundred seventy-four subjects (103 normal eyes and 371 glaucomatous eyes) were scanned to determine the RNFL thickness measurements using the Stratus OCT. Measurements were obtained twice during the same day. The standard deviation (SD) was used to compare the variability in RNFL thickness measurements of the normal subjects to that of the glaucomatous patients. Multivariate regression analysis was used to evaluate which covariates were independent predictors of SD in overall mean RNFL thickness.
The mean SD of all RNFL thickness measurements was larger in the glaucoma group except in one sector. In the multivariate regression analysis, the average signal strength (SS) and the relative SS change (difference in SS between initial and repeat scans, divided by initial SS) were independent predictors of the SD in the RNFL thickness measurements (partial R2 = 0.018, 0.013; p = 0.016, 0.040, respectively).
Glaucomatous eyes tend to be more variable than normal eyes in RNFL thickness measurement using the Straus OCT. The average SS and the relative SS changes appear to correlate with the variability in RNFL thickness measurement. Therefore, the results of the RNFL analysis should not be interpreted independently of these factors.
Glaucoma; Optical coherence tomography; Retinal nerve fiber layer thickness; Variability