The Association Between Clinical Features Seen on Fundus Photographs and Glaucomatous Damage Detected on Visual Fields and Optical Coherence Tomography Scans.

PURPOSE: To classify the appearance of the optic disc seen on fundus photographs of healthy subjects and patients with or suspected glaucoma whose diagnosis was based upon visual fields (VFs) and spectral-domain optical coherence tomography (sdOCT) results. PATIENTS AND METHODS: One eye of 100 patients with or suspected glaucoma and 62 healthy subjects were prospectively tested with 24-2 and 10-2 VF and macular and disc sdOCT cube scans. All eyes with or suspected glaucoma had a 24-2 mean deviation better than -6.0 dB and an abnormal appearing disc on stereophotographs. The retinal ganglion cell plus inner plexiform layer (RGC+) from the macular scans and the retinal nerve fiber layer (RNFL) from the macular and disc scans were segmented and converted to probabilities plots. An eye was considered "glaucoma" if the sdOCT probability plots showed an abnormality in a region that corresponded to a defect seen on the 24-2 and/or 10-2 VF total deviation plot. Similarly, an eye was considered "suspect" only if both the sdOCT and VF plots were normal. Healthy subjects (normal VFs and sdOCT) were classified as "controls" and used as reference for comparisons. Glaucoma specialists reviewed the stereophotographs and classified eyes based on the presence of signs suggestive of glaucomatous optic neuropathy. RESULTS: The pattern of clinical signs of glaucomatous optic neuropathy seen on stereophotographs was statistically different between glaucoma (P<0.001) and suspects (P<0.001) vs. controls and explained up to 68% of the total variance of the diagnosis based upon sdOCT and VFs. Vertical cup-to-disc>0.6, focal neuroretinal rim thinning, focal RNFL loss, and violation of the ISNT rule had the best performance to differentiate glaucoma and suspects from controls. Compared with the suspect group, glaucoma eyes (abnormal sdOCT and VF tests) were more likely to have vertical cup-to-disc>0.6 (92% vs. 69%, P=0.003), diffuse rim (53% vs. 9%, P<0.001) and RNFL (61% vs. 26%, P<0.001) thinning, and ß-zone parapapillary atrophy (68% vs. 17%, P<0.001). CONCLUSIONS: Focal and diffuse signs of glaucoma damage seen on stereophotographs often match damage shown on VFs and sdOCT. In addition, damage shown on VFs and sdOCT is often missed during clinical evaluation. Longitudinal studies ought to differentiate focal signs of glaucoma damage seen on stereophotography from false-positives or very early loss.

Central Glaucomatous Damage of the Macula Can Be Overlooked by Conventional OCT Retinal Nerve Fiber Layer Thickness Analyses.

PURPOSE: To assess the extent to which glaucomatous damage of the macula can be detected using the summary statistics of a commercial report based upon the circumpapillary retinal nerve fiber layer (cpRNFL) thickness obtained with frequency domain optical coherence tomography (fdOCT). METHODS: One hundred forty-three eyes of 143 open-angle glaucoma patients and suspects (56.4 ± 13.8 years) had 10-2 visual fields (VFs) and fdOCT macular and disc cube scans. RNFL and retinal ganglion cell plus inner plexiform layer thickness and probability maps were generated and combined with 10-2 VF information in a single-page, custom report previously described. Three graders evaluated these reports and classified each eye as "abnormal macula" or "normal macula." Commercially available fdOCT reports for cpRNFL thickness were generated using the automatic segmentation algorithm and norms from the machine. The ability of the reports to detect macular damage was analyzed in three ways: temporal quadrant (TQ) < 5%; TQ < 5% or clock hour 7 < 1% (TQ + CH7); and clock hours 7 through 10 with two sectors < 5% or one sector < 1% (CH7-10). RESULTS: Sixty-one (43%) eyes were classified "abnormal macula" and 41 (29%) as "normal macula"; the 10-2 VFs and OCT probability maps did not agree in the remaining eyes. Of the 61 abnormal eyes, the TQ criterion missed 47 (77%); TQ + CH7 missed 24 (39%); and CH7-10 missed 22 (36%). CONCLUSIONS: Conventional cpRNFL analyses on commercial OCT reports can miss macular (central field) damage. TRANSLATIONAL RELEVANCE: To detect glaucomatous damage of the macula, additional tests, such as macular cube scans and/or 10-2 VFs, should be performed.

Evaluation of the Structure-Function Relationship in Glaucoma Using a Novel Method for Estimating the Number of Retinal Ganglion Cells in the Human Retina.

PURPOSE: We developed a simple method for estimating the number of retinal ganglion cells (RGCs) in the human retina using optical coherence tomography (OCT), compared it to a previous approach, and demonstrated its potential for furthering our understanding of the structure-function relationship in glaucoma. METHODS: Swept-source (ss) OCT data and 10-2 visual fields (VFs) were obtained from 43 eyes of 36 healthy controls, and 50 eyes of 50 glaucoma patients and suspects. Using estimates of RGC density from the literature and relatively few assumptions, estimates of the number of RGCs in the macula were obtained based on ssOCT-derived RGC layer thickness measurements. RESULTS: The RGC estimates were in general agreement with previously published values derived from histology, whereas a prior method based on VF sensitivity did not agree as well with histological data and had significantly higher (P = 0.001) and more variable (P < 0.001) RGC estimates than the new method based on ssOCT. However, the RGC estimates of the new approach were not zero for extreme VF losses, suggesting that a residual, non-RGC contribution needs to be added. Finally, the new ssOCT-derived RGC estimates were significantly (P < 0.001 to P = 0.018) related to VF sensitivity (Spearman's ρ = 0.26-0.47), and, in contrast to claims made in prior studies, statistically significant RGC loss did not occur more often than statistically significant visual loss. CONCLUSIONS: The novel method for estimating RGCs yields values that are closer to histological estimates than prior methods, while relying on considerably fewer assumptions. Although the value added for clinical applications is yet to be determined, this approach is useful for assessing the structure-function relationship in glaucoma.

Relationship Between Pattern Electroretinogram, Frequency-Domain OCT, and Automated Perimetry in Chronic Papilledema From Pseudotumor Cerebri Syndrome.

PURPOSE: We evaluated the ability of transient pattern electroretinogram (PERG) parameters to differentiate between eyes with visual field (VF) loss and resolved papilledema from pseudotumor cerebri syndrome (PTC) and controls, to compare PERG and optical coherence tomography (OCT) with regard to discrimination ability, and to assess the correlation between PERG, frequency domain OCT (FD-OCT), and VF measurements. METHODS: The VFs and full-field stimulation PERGs based on 48 and 14-min checks were obtained from patients with PTC (n = 24, 38 eyes) and controls (n = 26, 34 eyes). In addition, FD-OCT peripapillary retinal nerve fiber layer (RNFL) and segmented macular layer measurements were obtained and correlation coefficients were determined. RESULTS: Compared to controls, PERG N95 and P50+N95 amplitude measurements with 48-minute checks were significantly reduced in eyes with resolved papilledema from PTC. Both PERG N95 amplitude and OCT parameters were able to discriminate papilledema eyes from controls with a similar performance. Significant correlations, ranging from 0.25 (P < 0.05) to 0.43 (P < 0.01) were found between PERG amplitude values and OCT-measured macular ganglion cell layer thickness, RNFL thickness, and total retinal thickness. The PERG amplitude also was significantly associated with VF sensitivity loss with correlation coefficients ranging from 0.24 (P < 0.05) and 0.35 (P < 0.01). CONCLUSIONS: The PERG measurements were able to detect neural loss in PTC eyes with resolved papilledema and were reasonably well correlated with OCT measurements and VF parameters. Thus, PERG may be a useful tool in the monitoring of retinal neural loss in eyes with active papilledema from PTC.

Evaluation of a Method for Estimating Retinal Ganglion Cell Counts Using Visual Fields and Optical Coherence Tomography.

PURPOSE: To evaluate the accuracy and generalizability of a published model that derives estimates of retinal ganglion cell (RGC) counts and relates structural and functional changes due to glaucoma. METHODS: Both the Harwerth et al. nonlinear model (H-NLM) and the Hood and Kardon linear model (HK-LM) were applied to an independent dataset of frequency-domain optical coherence tomography and visual fields, consisting of 48 eyes of 48 healthy controls, 100 eyes of 77 glaucoma patients and suspects, and 18 eyes of 14 nonarteritic anterior ischemic optic neuropathy (ION) patients with severe vision loss. Using the coefficient of determination R2, the models were compared while keeping constant the topographic maps, specifically a map by Garway-Heath et al. and a separate map by Harwerth et al., which relate sensitivity test stimulus locations to corresponding regions around the optic disc. Additionally, simulations were used to evaluate the assumptions of the H-NLM. RESULTS: Although the predictions of the HK-LM with the anatomically-derived Garway-Heath et al. map were reasonably good (R2 = 0.31-0.64), the predictions of the H-NLM were poor (R2 < 0) regardless of the map used. Furthermore, simulations of the H-NLM yielded results that differed substantially from RGC estimates based on histology from human subjects. Finally, the value-added of factors increasing the relative complexity of the H-NLM, such as assumptions regarding age- and stage-dependent corrections to structural measures, was unclear. CONCLUSIONS: Several of the assumptions underlying the H-NLM should be revisited. Studies and models relying on the RGC estimates of the H-NLM should be interpreted with caution.

A Test of a Model of Glaucomatous Damage of the Macula With High-Density Perimetry: Implications for the Locations of Visual Field Test Points.

PURPOSE: To use high-density perimetry to test a model of local glaucomatous damage to the macula (central visual field [VF]) and to assess the optimal placement of stimuli used to detect this damage. METHODS: Thirty-one eyes of 31 patients showing glaucomatous arcuate damage within the upper hemifield of the central 10° were tested with a customized VF with double the density of the 10-2 (2° grid) test. Individual plots of total deviation (TD) values were generated. A model, which predicts a "vulnerable macular region" (VMR) and a "less vulnerable macular region" (LVMR), was compared with the TD values without (standard model) and with (aligned model) scaling and rotating to align it with the patient's fovea-to-disc axis. Computer simulations assessed alternative VF locations for adding two points to the 6° grid pattern (e.g., 24-2 VF) typically used in the clinic. RESULTS: There were significantly more abnormal points in the VMR than in the LVMR. However, the aligned model did no better than the standard model in describing the data. The optimal locations for adding two points to the 24-2 (6° grid) test were (-1°, 5°) and (1°, 5°), both within the VMR. CONCLUSIONS: The model describes the region of the superior VF vulnerable to arcuate damage. TRANSLATIONAL RELEVANCE: The model can be used to determine the optimal locations for adding test points to the commonly used VF test pattern (24-2). It does not seem necessary to adjust the location of VF test points based upon interindividual differences in the fovea-to-disc axis.

On improving the use of OCT imaging for detecting glaucomatous damage.

AIMS: To describe two approaches for improving the detection of glaucomatous damage seen with optical coherence tomography (OCT). METHODS: The two approaches described were: one, a visual analysis of the high-quality OCT circle scans and two, a comparison of local visual field sensitivity loss to local OCT retinal ganglion cell plus inner plexiform (RGC+) and retinal nerve fibre layer (RNFL) thinning. OCT images were obtained from glaucoma patients and suspects using a spectral domain OCT machine and commercially available scanning protocols. A high-quality peripapillary circle scan (average of 50), a three-dimensional (3D) scan of the optic disc, and a 3D scan of the macula were obtained. RGC+ and RNFL thickness and probability plots were generated from the 3D scans. RESULTS: A close visual analysis of a high-quality circle scan can help avoid both false positive and false negative errors. Similarly, to avoid these errors, the location of abnormal visual field points should be compared to regions of abnormal RGC+ and RNFL thickness. CONCLUSIONS: To improve the sensitivity and specificity of OCT imaging, high-quality images should be visually scrutinised and topographical information from visual fields and OCT scans combined.

Evaluation of inner retinal layers in eyes with temporal hemianopic visual loss from chiasmal compression using optical coherence tomography.

PURPOSE: We measured macular inner retinal layer thicknesses using frequency-domain optical coherence tomography (fd-OCT) and correlated these measures with visual field (VF) in eyes with temporal hemianopia from chiasmal compression and band atrophy (BA) of the optic nerve. METHODS: Macular fd-OCT scans and VFs were obtained from 33 eyes of 33 patients with temporal hemianopia and 36 control eyes. The macular retinal nerve fiber layer (mRNFL), combined retinal ganglion cell and inner plexiform layers (RGCL+), and the inner nuclear layer (INL) were segmented. Measurements were averaged for each macula quadrant. Scans were assessed qualitatively for microcysts in the INL. The VF was estimated from the central 16 test points. The two groups were compared. Correlations between VF and OCT measurements were assessed. RESULTS: The mRNFL, RGCL+, and total retinal (TR) macular thickness measurements were significantly smaller in BA eyes than controls. In the nasal quadrants, INL measurements were significantly greater in BA eyes than controls. The mRNFL and RGCL+ measurements had greater discrimination ability than TR measurements in the temporal quadrants. A significant correlation was found between most OCT parameters and their corresponding VF parameters. The strongest association was observed between RNFL and RGCL+ thickness, and VF loss in the corresponding area. The INL microcysts were found in seven eyes with BA, but not in controls. CONCLUSIONS: Band atrophy leads to mRNFL and RGCL+ thinning, and INL thickening, and mRNFL and RGCL+ measurements are correlated strongly with VF loss. Segmented macular thickness measurements may be useful for quantifying neuronal loss in chiasmal compression.

Improving glaucoma detection using spatially correspondent clusters of damage and by combining standard automated perimetry and optical coherence tomography.

PURPOSE: To improve the detection of glaucoma, techniques for assessing local patterns of damage and for combining structure and function were developed. METHODS: Standard automated perimetry (SAP) and frequency-domain optical coherence tomography (fdOCT) data, consisting of macular retinal ganglion cell plus inner plexiform layer (mRGCPL) as well as macular and optic disc retinal nerve fiber layer (mRNFL and dRNFL) thicknesses, were collected from 52 eyes of 52 healthy controls and 156 eyes of 96 glaucoma suspects and patients. In addition to generating simple global metrics, SAP and fdOCT data were searched for contiguous clusters of abnormal points and converted to a continuous metric (pcc). The pcc metric, along with simpler methods, was used to combine the information from the SAP and fdOCT. The performance of different methods was assessed using the area under receiver operator characteristic curves (AROC scores). RESULTS: The pcc metric performed better than simple global measures for both the fdOCT and SAP. The best combined structure-function metric (mRGCPL&SAP pcc, AROC = 0.868 ± 0.032) was better (statistically significant) than the best metrics for independent measures of structure and function. When SAP was used as part of the inclusion and exclusion criteria, AROC scores increased for all metrics, including the best combined structure-function metric (AROC = 0.975 ± 0.014). CONCLUSIONS: A combined structure-function metric improved the detection of glaucomatous eyes. Overall, the primary sources of value-added for glaucoma detection stem from the continuous cluster search (the pcc), the mRGCPL data, and the combination of structure and function.

Prevalence and nature of early glaucomatous defects in the central 10° of the visual field.

IMPORTANCE: The macula is essential for visual functioning and is known to be affected even in early glaucoma. However, little is currently understood about the prevalence and nature of central vision loss in early glaucoma. OBJECTIVE: To determine the prevalence and characteristics of visual field (VF) defects in the central 10° in glaucoma suspects and patients with mild glaucoma using a prospective design. DESIGN, SETTING, AND PARTICIPANTS: This prospective observational cohort study was conducted at an outpatient glaucoma specialty clinic. One hundred eyes from 74 patients with glaucomatous optic neuropathy and a 24-2 VF with mean deviation better than -6 dB were prospectively studied and tested with a 10-2 test. MAIN OUTCOMES AND MEASURES: Reliable: VF hemifields were classified as abnormal based on a cluster criterion, and abnormal 10-2 VFs were categorized based on the pattern of abnormal points: arcuatelike, widespread, or other. In addition, at each point of the 10-2 VF, the total deviation values were averaged across eyes and the number of abnormal points with total deviation values below a specific criterion level were calculated. RESULTS There appeared to be as many abnormal 10-2 hemifields (53%) as abnormal 24-2 hemifields (59%). Of the eyes with normal 24-2 hemifields, 16% were classified as abnormal when the 10-2 test was used. Of the abnormal 10-2 hemifields, 68%, 8%, and 25% were arcuatelike, widespread, and other, respectively. The average total deviation values and number of abnormal points plots revealed superior VF defects that were deeper and closer to fixation than those in the inferior VF. CONCLUSIONS AND RELEVANCE: The 10-2 VF was abnormal in nearly as many hemifields as was the 24-2 VF, including some with normal 24-2 VF, suggesting that the 24-2 test is not optimal for detecting early damage of the macula. The pattern of the defects was in agreement with a recent model of macular damage.

Early glaucoma involves both deep local, and shallow widespread, retinal nerve fiber damage of the macular region.

PURPOSE: To better understand the nature of early glaucomatous damage of the macula by comparing the results from 10-2 visual fields, optical coherence tomography (OCT) macular cube scans, and OCT circumpapillary circle scans. METHODS: One eye of each of 66 glaucoma patients or suspects, with a mean deviation (MD) on the 24-2 visual field (VF) test of better than -6 decibels (dB), was prospectively tested with 10-2 VFs and OCT macular cube and circumpapillary circle scans. Thickness and probability maps of the retinal ganglion cell plus inner plexiform (RGC+) layers were generated. A hemifield was considered abnormal if both the macular RGC+ and the 10-2 probability plots were abnormal (cluster criteria). The thickness plots of the circumpapillary retinal nerve fiber layer (RNFL) were analyzed in the context of a model that predicted the region of the disc associated with macular damage. RESULTS: Twenty-seven hemifields (20 eyes) had abnormal 10-2 and RGC+ probability plots: 7 in upper VF/inferior retina, 6 in lower VF/superior retina, and 7 in both hemifields. Both shallow widespread and deep local thinning of the circumpapillary RNFL were observed. The local defects were more common and closer to fixation in the upper VF/inferior retina as predicted. CONCLUSIONS: A model of glaucomatous damage of the macula predicted the location of both the widespread and local defects in the temporal and inferior disc quadrants. Optical coherence tomography scans of the circumpapillary RNFL and the macular RGC+ layer can aid in the identification of these defects and help in the interpretation of 24-2 and 10-2 VF tests.

Modifying the Conventional Visual Field Test Pattern to Improve the Detection of Early Glaucomatous Defects in the Central 10°

PURPOSE: To simulate modified versions of the 24-2 (6° grid) visual field (VF) test pattern by adding points from the 10-2 (2° grid) test pattern, and to assess their ability to detect early glaucomatous defects in the central 10°. METHODS: One hundred forty-four eyes of 144 glaucoma patients and suspects with 24-2 mean deviations better than -6 dB were tested with 10-2 and 24-2 VFs. Based upon both 10-2 VF and optical coherence tomography probability plots, 63 hemifields were defined as abnormal, while 121 hemifields were defined as normal. Three modified 24-2 VF test patterns, called 24-2 +4, 24-2 +16 (Even), and 24-2 +16 (Empirical), were simulated by adding 4 or 16 test points from the 10-2 VF. RESULTS: Based upon the number of abnormal points (P ≤ 5%), the area under the ROC curves (AROC scores) of the three modified 24-2 VFs were significantly greater than that of the 24-2 VF for both the upper and lower VF. For a specificity of 85%, the number of true positives was 25 (24-2), 30 (24-2 +4), 31 (24-2 +16, even), and 32 (24-2 +16, empirical) of 34 total true positives for the upper VF and 23, 26, 27, and 28 of 29 for the lower VF. CONCLUSIONS: Adding points from the 10-2 test pattern to the 24-2 test pattern significantly improved its ability to detect macular defects without employing more test points than a single 10-2 test. TRANSLATIONAL RELEVANCE: Additional central points should be added to the 24-2 pattern to improve the detection of macular damage.

Evaluation of a One-Page Report to Aid in Detecting Glaucomatous Damage.

PURPOSE: We assessed the use of a customized, one-page structure + function report for aiding in detection of glaucomatous damage. METHODS: Two individuals (report specialists), experienced in analyzing optical coherent tomography (OCT) and visual field (VF) results, examined a customized one-page report for 50 eyes from 50 patients who either had glaucoma or were glaucoma suspects. The report contained key features of OCT scans with VF information. All patients had 24-2 VFs with a mean deviation (MD) better than -6 dB. The report specialists classified each hemifield and eye as either glaucomatous or nonglaucomatous based upon only the customized report, either without (phase 1) or with (phase 2) 24-2 VF information included on the report. Their results were compared to the classifications made by 3 ophthalmologists (glaucoma specialists) based upon traditional measures, namely stereo photographs, 24-2 VFs, and a commercially available, OCT disc scan report. RESULTS: The two report specialists agreed on all but one eye and four hemifields in phase 1, and on all eyes and all but one hemifield in phase 2. In phase 2, they judged 31 eyes abnormal. Of these 31 eyes, 30 were judged abnormal by all three glaucoma specialists and the 31st by two of the three. Without the VF information (phase 1), one report specialist classified 1, and the other 2, of these 31 "abnormal" eyes as normal. CONCLUSIONS: When using the one-page report, the experienced readers showed excellent inter-rater repeatability and diagnostic ability relative to glaucoma specialists. TRANSLATIONAL RELEVANCE: This condensed report may help the clinician assess glaucomatous damage.

The locations of circumpapillary glaucomatous defects seen on frequency-domain OCT scans.

PURPOSE: To examine the locations of local glaucomatous damage around the optic disc as seen in the circumpapillary retinal nerve fiber layer (RNFL) on frequency domain optical coherence tomography (fdOCT). METHODS: Optic disc fdOCT volume scans from 54 healthy control eyes and 114 patient eyes, classified as suspected or mild glaucoma, were analyzed. All patient eyes had 24-2 visual fields (VFs) with mean deviations better than -5.5 dB. By hand-correcting automated segmentation, the RNFL thickness profile was obtained for a circumpapillary circle. RNFL defects were defined as regions where the patient's RNFL thickness fell below the 99% confidence limit of control values. The location of a defect was defined as the point of greatest difference between the patient's thickness and the 99% limit. The locations of major blood vessels (BVs) were marked, and separated into superior-nasal (SN), superior-temporal (ST), inferior-temporal (IT), and inferior-nasal (IN) groups. RESULTS: Of the 114 patient eyes, 45 exhibited a total of 75 RNFL defects. The locations of these defects clustered around the ST, SN, and IT, but not the IN BVs. CONCLUSIONS: The absence of defects in the IN region indicates that the locations of local defects are not simply related to either BV location or RNFL thickness. The local defects in the ST and IT regions can be related to arcuate defects seen on 24-2 and 10-2 VFs. However, the defects in the SN region suggest the presence of VF defects that may be overlooked because they fall largely outside the 24-2 test grid.

Pattern electroretinogram in neuromyelitis optica and multiple sclerosis with or without optic neuritis and its correlation with FD-OCT and perimetry.

PURPOSE: To evaluate the ability of transient pattern electroretinogram (PERG) parameters to differentiate between eyes of patients with neuromyelitis optica (NMO), longitudinally extensive transverse myelitis (LETM), multiple sclerosis with optic neuritis (MS + ON), multiple sclerosis without optic neuritis (MS - ON), and controls, to compare PERG and OCT with regard to discrimination ability, and to assess the correlation between PERG, FD-OCT, and visual field measurements (VFs). METHODS: Visual field measurements and full-field stimulation PERGs based on both 48- and 14-min checks were obtained from patients with MS (n = 28), NMO (n = 20), LETM (n = 18), and controls (n = 26). In addition, FD-OCT peripapillary retinal nerve fiber layer (RNFL) and segmented macular layer measurements were obtained and their correlation coefficients were determined. RESULTS: Compared to controls, PERG amplitude measurements were significantly reduced in eyes with NMO and MS + ON, but not in eyes with LETM and MS - ON. PERG amplitudes were significantly smaller in NMO and MS + ON eyes than in MS - ON eyes. PERG and OCT performance was similar except in NMO eyes where macular thickness parameters were more efficient at detecting abnormalities. A significant correlation was found between N95 amplitude values and OCT-measured macular ganglion cell layer thickness, total retinal thickness, and temporal peripapillary RNFL thickness. PERG amplitude was also significantly associated with VF sensitivity loss. No statistically significant difference was observed with regard to the best-performing parameters of the two methods. CONCLUSIONS: Pattern electroretinogram measurements were able to detect RNFL loss in MS + ON and NMO eyes, with a performance comparable to OCT. PERG amplitude measurements were reasonably well correlated with OCT-measured parameters.

Detecting glaucoma with visual fields derived from frequency-domain optical coherence tomography.

PURPOSE: To compare the assessment of glaucomatous damage based on visual fields (VFs) derived from frequency-domain optical coherence tomography (OCT) to actual VFs obtained from static automated perimetry. METHODS: A total of 84 eyes from 84 glaucoma patients or suspects and 128 eyes from 128 healthy subjects were included. The retinal ganglion cell (RGC) and retinal nerve fiber layer (RNFL) thicknesses measured with macular and disc RNFL cube scans were combined and decomposed into 48 principal components (PCs). For each eye, an OCT to VF transformation map was built using multiple linear regression (MLR) and the OCT and VF data from the other eyes. Using this transformation map, the combined 24-2- and 10-2-derived VF for this eye was then obtained. RESULTS: With 98.0% specificity, the sensitivity of the derived VF reached 78.0% for all hemifields, whereas 74.4% of the actual VF hemifields were classified as abnormal. The agreement between the derived and the actual VFs was 82.2%. For each VF location, the derived VF values were linearly related to the actual values. CONCLUSIONS: The derived VF based on the OCT data appears as sensitive as the actual VF for detecting glaucomatous damage. Because the derived and actual VFs should have largely independent sources of variability, the combination of the two should provide a more powerful diagnostic tool.

Glaucomatous damage of the macula.

There is a growing body of evidence that early glaucomatous damage involves the macula. The anatomical basis of this damage can be studied using frequency domain optical coherence tomography (fdOCT), by which the local thickness of the retinal nerve fiber layer (RNFL) and local retinal ganglion cell plus inner plexiform (RGC+) layer can be measured. Based upon averaged fdOCT results from healthy controls and patients, we show that: 1. For healthy controls, the average RGC+ layer thickness closely matches human histological data; 2. For glaucoma patients and suspects, the average RGC+ layer shows greater glaucomatous thinning in the inferior retina (superior visual field (VF)); and 3. The central test points of the 6° VF grid (24-2 test pattern) miss the region of greatest RGC+ thinning. Based upon fdOCT results from individual patients, we have learned that: 1. Local RGC+ loss is associated with local VF sensitivity loss as long as the displacement of RGCs from the foveal center is taken into consideration; and 2. Macular damage is typically arcuate in nature and often associated with local RNFL thinning in a narrow region of the disc, which we call the macular vulnerability zone (MVZ). According to our schematic model of macular damage, most of the inferior region of the macula projects to the MVZ, which is located largely in the inferior quadrant of the disc, a region that is particularly susceptible to glaucomatous damage. A small (cecocentral) region of the inferior macula, and all of the superior macula (inferior VF), project to the temporal quadrant, a region that is less susceptible to damage. The overall message is clear; clinicians need to be aware that glaucomatous damage to the macula is common, can occur early in the disease, and can be missed and/or underestimated with standard VF tests that use a 6° grid, such as the 24-2 VF test.

Evaluation of inner retinal layers in patients with multiple sclerosis or neuromyelitis optica using optical coherence tomography.

PURPOSE: To evaluate the thickness of the inner retinal layers in the macula using frequency-domain optical coherence tomography (fd-OCT) in patients with demyelinating diseases. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 301 eyes of 176 subjects were evaluated. Subjects were divided in 5 different groups: controls, neuromyelitis optica (NMO), longitudinally extensive transverse myelitis (LETM), multiple sclerosis with a history of optic neuritis (MS-ON), and multiple sclerosis without a history of optic neuritis (MS non-ON). METHODS: The individual layers from macular fd-OCT cube scans were segmented with an automated algorithm and then manually hand-corrected. For each scan, we determined the thickness of the retinal nerve fiber layer (RNFL), the combined retinal ganglion cell and inner plexiform layers (RGCL+), and the inner nuclear layer (INL). MAIN OUTCOME MEASURES: Macular RNFL, RGCL+, and INL thickness. RESULTS: The RNFL was significantly thinner than in controls for all patient groups (P ≤ 0.01). Macular RGCL+ thickness was significantly thinner than in controls for the NMO, MS-ON, and MS non-ON groups (P<0.001 for the 3 groups). The INL thickness was significantly thicker than in controls for the patients with NMO (P = 0.003) and LETM (P = 0.006) but not for those with MS-ON or MS non-ON. Although the RNFL and RGCL+ were not significantly different between the NMO and MS-ON groups, the patients with NMO had a significantly thicker INL than the patients with MS-ON (P = 0.02). CONCLUSIONS: Macular RNFL and RGCL+ demonstrate axonal and neural loss in patients with MS, either with or without ON, and in patients with NMO. In addition, the INL thickening occurs in patients with NMO and patients with LETM, and study of this layer may hold promise for differentiating between NMO and MS.

The Nature of Macular Damage in Glaucoma as Revealed by Averaging Optical Coherence Tomography Data.

PURPOSE: To better understand the nature of glaucomatous damage, especially to the macula, the inner retinal thickness maps obtained with frequency domain optical coherence tomography (fdOCT) were averaged. METHODS: Frequency domain optical coherence tomography macular and optic disc cube scans were obtained from 54 healthy eyes and 156 eyes with glaucomatous optic neuropathy. A manually corrected algorithm was used for layer segmentation. Patients' eyes were grouped both by mean deviation (MD) and hemifield classification using standard categories and 24-2 (6° grid) visual fields (VFs). To obtain average difference maps, the thickness of retinal nerve fiber (RNF) and retinal ganglion cell plus inner plexiform (RGC+) layers were averaged and subtracted from the average control values. RESULTS: On the average difference maps, RGC+ and RNF layer thinning was seen in the patient groups with VFs classified as normal. The pattern of the thinning was the same, but the degree of thinning increased with decreased MD and with classification category (from normal to arcuate). This RGC+ thinning was largely within the central four points of the 24-2 (6° grid) field, after correcting for RGC displacement. CONCLUSION: 1. VF categories represent different degrees of the same pattern of RGC+ and RNFL layer thinning. 2. RGC+ damage occurs in the central macula even in patients with VFs classified as normal. 3. The 6° grid (24-2) pattern is not optimally designed to detect macular damage. 4. A schematic model of RGC projections is proposed to explain the pattern of macular loss, including the greater vulnerability of the inferior retinal region. TRANSLATIONAL RELEVANCE: The 24-2 is not an optimal test pattern for detecting or following glaucomatous damage. Further, we suggest clinical fdOCT reports include RGC+ and RNFL probability plots combined with VF information.

Retinal ganglion cell layer thickness and local visual field sensitivity in glaucoma.

OBJECTIVE: To compare loss in sensitivity measured using standard automated perimetry (SAP) with local retinal ganglion cell layer (RGC) thickness measured using frequency-domain optical coherence tomography in the macula of patients with glaucoma. METHODS: To compare corresponding locations of RGC thickness with total deviation (TD) of 10-2 SAP for 14 patients with glaucoma and 19 controls, an experienced operator hand-corrected automatic segmentation of the combined RGC and inner plexiform layer (RGC+IPL) of 128 horizontal B-scans. To account for displacement of the RGC bodies around the fovea, the location of the SAP test points was adjusted to correspond to the location of the RGC bodies rather than to the photoreceptors, based on published histological findings. For analysis, RGC+IPL thickness vs SAP (TD) data were grouped into 5 eccentricities, from 3.4° to 9.7° radius on the retina with respect to the fovea. RESULTS: The RGC+IPL thickness correlated well with SAP loss within approximately 7.2° of the fovea (Spearman ρ = 0.71-0.74). Agreement was worse (0.53-0.65) beyond 7.2°, where the normal RGC layer is relatively thin. A linear model relating RGC+IPL thickness to linear SAP loss provided a reasonable fit for eccentricities within 7.2°. CONCLUSION: In the central 7.2°, local RGC+IPL thickness correlated well with local sensitivity loss in glaucoma when the data were adjusted for RGC displacement.