Retinal Nerve Fiber Layer Bundles Research Articles

Structure–function assessment in glaucoma based on perimetric sensitivity and en face optical coherence tomography images of retinal nerve fiber bundles

Many studies have assessed structure–function relations in glaucoma, but most without topographical comparison across the central 30°. We present a method for assessing structure–function relations with en face images of retinal nerve fiber layer (RNFL) bundles allowing topographical comparison across much of this retinal area. Forty-four patients with glaucoma (median age 61 years) were recruited and tested with Optical Coherence Tomography (OCT) and perimetry. Six rectangular volume scans were gathered, and then montaged to provide en face views of the RNFL bundles. We calculated the proportion of locations showing a perimetric defect that also showed an en face RNFL defect; and the proportion of locations falling on an RNFL defect that also showed a perimetric defect. A perimetric defect for a location was defined as a total deviation (TD) value equal to or deeper than -4 dB. We found that the median (IQR) number of locations with abnormal RNFL bundle reflectance that also had abnormal TD was 78% (60%) and for locations with abnormal TD that also had abnormal RNFL bundle reflectance was 75% (44%). We demonstrated a potential approach for structure–function assessment in glaucoma by presenting a topographic reflectance map, confirming results of previous studies and including larger retinal regions.

Adaptive optics scanning laser ophthalmoscopy may support early diagnosis of glaucoma.

To compare image characteristics of retinal nerve fiber layer (RNFL) between glaucoma patients and healthy controls using adaptive optics scanning laser ophthalmoscopy (AOSLO). This was a cross-sectional pilot study with two groups: a glaucoma group with patients with moderate or severe glaucoma as per the Hodapp-Parrish-Anderson classification system and a control group with healthy individuals. The optic nerve damage in moderate glaucoma was predominantly located in only one hemisphere; the other hemisphere was un- or minimally affected on optical coherence tomography and automated perimetry and is referred to as early glaucoma. The structure of RNFL bundles and gain (%) in RNFL images with mean pixel values between 15 and 35 were analyzed. Imaging was performed one degree away from the optic disc margin at two and four cardinal clock positions in the glaucoma and control groups, respectively. The field of view was 1.3° at 2.3 μ resolution. We studied one eye per participant. There were 11 glaucoma patients and 7 healthy controls. Imaging was successful at 88% of the locations in controls and early glaucoma; the reflectivity differed significantly (0.51 and 0.56, respectively, P < 0.001) but not the structure of RNFL bundles (Cohen's Kappa 0.11) between them. In patients with moderate and severe glaucoma, imaging was successful only at 46% of the locations; RNFL bundles were not discernible, and RNFL reflectivity did not differ from those with early glaucoma (P < 0.11). The recorded gain (%) of RNFL images obtained using AOSLO could be an objective indicator of early glaucoma.

Customizing Perimetric Locations Based on En Face Images of Retinal Nerve Fiber Bundles With Glaucomatous Damage

PurposePrior studies suggested the use of customized perimetric locations in glaucoma; these studies were limited by imaging only the superficial depths of the retinal nerve fiber layer (RNFL) and by prolonged perimetric testing. We aimed to develop a rapid perimetric test guided by high-resolution images of RNFL bundles.MethodsWe recruited 10 patients with glaucoma, ages 56 to 80 years, median 68 years, and 10 controls, ages 55 to 77 years, median 68 years. The patients were selected based on discrepancies between locations of glaucomatous damage for perimetric and structural measures. Montaging was used to produce optical coherence tomography en face images of the RNFL covering much of the 24-2 grid locations. In experiment 1, we presented the Goldmann size III stimulus at preselected retinal locations of glaucomatous damage, using just two contrasts. In experiment 2, we developed an elongated sinusoidal stimulus, aligned within the defect, to measure contrast sensitivities; abnormalities were defined based on lower 95% reference limits derived from the controls.ResultsThe percentage of predicted locations where size III was not seen at 28 dB ranged from 16% to 80%, with a median of 48%. Contrast sensitivity for the sinusoidal stimulus was below the 95% reference range for 37 of 44 stimuli aligned within the defects.ConclusionsWe developed methods for rapid perimetric testing guided by en face images of the RNFL bundles in patients with glaucoma. Results indicated ganglion cell damage under all of the visible RNFL defects.Translational RelevanceCustomized perimetric locations have potential to improve clinical assessment of glaucoma.

Adaptive optics optical coherence tomography in glaucoma.

Since the introduction of commercial optical coherence tomography (OCT) systems, the ophthalmic imaging modality has rapidly expanded and it has since changed the paradigm of visualization of the retina and revolutionized the management and diagnosis of neuro-retinal diseases, including glaucoma. OCT remains a dynamic and evolving imaging modality, growing from time-domain OCT to the improved spectral-domain OCT, adapting novel image analysis and processing methods, and onto the newer swept-source OCT and the implementation of adaptive optics (AO) into OCT. The incorporation of AO into ophthalmic imaging modalities has enhanced OCT by improving image resolution and quality, particularly in the posterior segment of the eye. Although OCT previously captured in-vivo cross-sectional images with unparalleled high resolution in the axial direction, monochromatic aberrations of the eye limit transverse or lateral resolution to about 15-20μm and reduce overall image quality. In pairing AO technology with OCT, it is now possible to obtain diffraction-limited resolution images of the optic nerve head and retina in three-dimensions, increasing resolution down to a theoretical 3μm3. It is now possible to visualize discrete structures within the posterior eye, such as photoreceptors, retinal nerve fiber layer bundles, the lamina cribrosa, and other structures relevant to glaucoma. Despite its limitations and barriers to widespread commercialization, the expanding role of AO in OCT is propelling this technology into clinical trials and onto becoming an invaluable modality in the clinician's arsenal.

Details of Glaucomatous Damage Are Better Seen on OCT En Face Images Than on OCT Retinal Nerve Fiber Layer Thickness Maps.

High-resolution images of glaucomatous damage to the retinal nerve fiber layer (RNFL) were obtained with an adaptive optics-scanning light ophthalmoscope (AO-SLO) and used as a basis for comparisons between en face slab images and thickness maps derived from optical coherence tomography (OCT) scans. Wide-field (9 × 12 mm) cube scans were obtained with swept-source OCT (DRI-OCT) from six eyes of six patients. All eyes had a deep defect near fixation as seen on a 10-2 visual field test. Optical coherence tomography en face images, based on the average reflectance intensity, were generated (ATL 3D-Suite) from 52-μm slabs just below the vitreal border of the inner limiting membrane. The RNFL thickness maps were generated from the same OCT data. Both were compared with the AO-SLO peripapillary images that were previously obtained. On AO-SLO images, three eyes showed small regions of preserved and/or missing RNFL bundles within the affected region. Details in these regions were seen on the OCT en face images but not on the RNFL thickness maps. In addition, in the healthier hemi-retinas of two eyes, there were darker, arcuate-shaped regions on en face images that corresponded to abnormalities seen on AO-SLO. These were not seen on RNFL thickness maps. Details of local glaucomatous damage, missing or easily overlooked on traditional OCT RNFL thickness analysis used in clinical OCT reports, were seen on OCT en face images based on the average reflectance intensity. While more work is needed, it is likely that en face slab imaging has a role in the clinical management of glaucoma.

Retinal Nerve Fiber Layer Imaging with Spectral-Domain Optical Coherence Tomography: Interpreting the RNFL Maps in Healthy Myopic Eyes

To investigate the association between the distribution profile of the retinal nerve fiber layer (RNFL) bundles and myopia and its impact on interpretation of the RNFL map imaged by a spectral-domain optical coherence tomography (SD-OCT). the RNFL of 189 myopic eyes from 103 normal healthy myopic participants was imaged by an SD-OCT. The angle between the long axes of the superotemporal and inferotemporal RNFL bundles determined in the RNFL thickness map (the RNFL distribution angle) and the abnormal area in the RNFL thickness deviation map were measured. The associations between the RNFL distribution angle and the axial length/spherical error, and between the area of abnormal RNFL measurement and each of the following: axial length, spherical error, RNFL distribution angle, average RNFL thickness, optic disc area, and signal strength were analyzed with linear mixed models. The RNFL distribution angle decreased with the axial length (P < 0.011). In the univariate analysis, the area of abnormal RNFL measurement was positively associated with the axial length (P = 0.001); and negatively associated with the RNFL distribution angle (P < 0.001), average RNFL thickness (P < 0.001), optic disc area (P ≤ 0.001), and signal strength (P = 0.026). In the multivariate analysis, the area of abnormal RNFL measurement was negatively associated with the RNFL distribution angle independent of other covariates. The superotemporal and inferotemporal RNFL bundles converged temporally with increasing myopia, which was associated with an increase in area of abnormal RNFL measurement. The interpretation of the RNFL thickness map in myopic eyes requires careful consideration of the distribution pattern of the RNFL bundles.

Pointwise Rates of Visual Field Progression Cluster according to Retinal Nerve Fiber Layer Bundles

To explore whether pointwise rates of visual field progression group together in patterns consistent with retinal nerve fiber layer (RNFL) bundles. Three hundred eighty-nine eyes of 309 patients from the Advanced Glaucoma Intervention Study with ≥6 years of follow-up and ≥12 reliable visual field exams were selected. Linear and exponential regression models were used to estimate pointwise rates of change over time. Clustering of pointwise rates of progression was investigated with hierarchical cluster analysis using Pearson's correlation coefficients as distance measure and an average linkage scheme for building the hierarchy with cutoff value of r > 0.7. The average mean deviation (±SD) was -10.9 (±5.4). The average (±SD) follow-up time and number of visual field exams were 8.1 (±1.1) years and 15.7 (±3.0), respectively. Pointwise rates of progression across the visual field grouped into clusters consistent with anatomic patterns of RNFL bundles with both linear (10 clusters) and exponential (six clusters) regression models. One hundred forty-four (37%) eyes progressed according to the two-omitting pointwise linear regression model. ointwise rates of change in glaucoma patients cluster into regions consistent with RNFL bundle patterns. This finding validates the clinical significance of such pointwise rates. The correlations among pointwise rates of change can be used for spatial filtering purposes, facilitating detection or prediction of glaucoma progression.

Retinal Nerve Fiber Layer Defect and Cerebral Small Vessel Disease

To determine whether retinal nerve fiber layer defect (RNFLD) is associated with cerebral small vessel diseases (SVDs) and to identify risk factors for RNFLD. A total of 4421 Korean subjects who underwent health checkups including brain magnetic resonance imaging (MRI) and fundus photography between January 2008 and October 2009 were included in this study. Co-morbid systemic diseases including hypertension, diabetes mellitus, and stroke or ocular diseases were evaluated using detailed questionnaires and medical records. Two experienced ophthalmologists assessed RNFLD on fundus photographs, according to the definition that describes the condition as marked thinning or absence of retinal nerve fiber layer bundles. RNFLD was detected in 238 of 4395 eligible subjects, and the estimated prevalence was 5.4%. Multivariate regression analysis results showed the prevalence of RNFLD to be significantly higher in hypertensive subjects (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.28-2.34), in those with cerebral SVD based on MRI (OR, 1.58; 95% CI, 1.17-2.12), and in male (OR, 1.47; 95% CI, 1.10-1.96) and older subjects (OR, 1.02; 95% CI, 1.00-1.03). Among the cases of cerebral SVD, white matter lesions (WMLs) were associated with RNFLD, whereas lacunar infarctions were not significantly associated with it. The results indicate that RNFLD may be related to the presence of cerebral SVD, particularly WMLs. Furthermore, being older and male and having hypertension increase the risk of RNFLD.

Structure and Function in Glaucoma: The Relationship between a Functional Visual Field Map and an Anatomic Retinal Map

To examine the relationship between an anatomic map relating the retinal nerve fiber layer (RNFL) distribution to the optic nerve head and a functional map derived from the interpoint correlation of raw sensitivities in visual field (VF) testing. Previously, interpoint correlations were generated for all possible pairs of VF test points in a dataset of 98,821 Humphrey VF test results taken from the Moorfields Eye Hospital archive. The relationship between these correlations and the physical distance between the VF test point pairs was evaluated by Pearson's correlation coefficient and multiple regression analysis. The distance between the pairs of VF test points was calculated in two ways. First, the anatomic map was used to estimate the angular distance at the optic nerve head (ONH), between the RNFL bundles corresponding to the VF test points in each pair (ONHd). Second, the retinal distance between pairs of test points was calculated from the Humphrey VF template (RETd). A best-fit model for predicting functional correlation (FC) from ONHd and RETd was constructed and used to formulate a filter incorporating the anatomic-functional correlation data. All scatterplots showed a negative association between interpoint retinal sensitivity correlation values and distance between points: ONHd (R2 = 0.60) and RETd (R2 = 0.33). The raw sensitivity correlation values could be predicted from a multiple regression model using ONHd, RETd, and a combined interaction of ONHd and RETd (R2 = 0.75, P < 0.00001). The construction of a new filter was based on the equation FC = 0.9325 - (0.0029 . ONHd) - (0.0077 . RETd) + (0.0001 . ONHd . RETd). A good level of association was observed between the strength of correlation between points in the VF and the relative location of those test points in the peripheral retina and in corresponding RNFL bundles at the ONH. These results help to validate the relationship between structure and function and may be of use in the further refinement of physiologically derived VF filters to reduce measurement noise.

The histology of retinal nerve fiber layer bundles and bundle defects.

The fiber bundle striations recognized clinically in normal monkey eyes appear to be bundles of axons compartmentalized within glial tunnels formed by Müller's-cell processes, when viewed histologically. The dark boundaries that separate individual bundles are the broadened foot endings of these cells near the inner surface of the retina. Within one week after focal retinal photocoagulation, characteristic fundus changes could be seen in experimental eyes. In histologic sections of the involved retina, there was marked cystic degeneration of the retinal nerve fiber layer. Within one month, atrophy of distal axon segments was complete. With the drop-out of damaged axons and thinning of individual fiber bundles, retinal striations became less prominent. The resulting fundus picture in these experimental eyes is similar to fiber bundle defects that can be seen clinically in various neuro-ophthalmic disorders.