Diagnostic capability of a linear discriminant function applied to a novel Spectralis OCT glaucoma-detection protocol.

BACKGROUND: Bruch membrane opening-minimum rim width (BMO-MRW) assessment offers a new diagnostic use in glaucoma patients of the Glaucoma Module Premium Edition (GMPE) available for the Spectralis optical coherence tomography (OCT) system. The objective of our research was to evaluate the diagnostic benefits of examining BMO-MRW and peripapillary retinal nerve fibre layer (pRNFL) readings acquired with Spectralis OCT to distinguish between healthy and mild glaucoma patients, comparing those readings with the standard pRNFL application. Moreover, we investigated whether using a particular combination of BMO-MRW and pRNFL parameters with a linear discriminant function (LDF) could further enhance glaucoma diagnosis. METHODS: One hundred thirty-six eyes from 136 individuals were incorporated into this observational, prospective cross-sectional study: 68 mild primary open-angle glaucoma (POAG) patients according to the Hodapp-Parrish-Anderson criteria (mean deviation between 0 and - 6 dB) and 68 healthy control subjects selected by Propensity Score Matching. MRW and pRNFL thickness around the disc (diameters: 3.5 mm, 4.1 mm, and 4.7 mm) were obtained using the BMO-MRW protocol, and pRNFL thickness at 3.5 mm was obtained with the standard glaucoma application. The group data were contrasted. One sample was chosen at random to develop the LDF (teaching set: 34 healthy subjects and 34 POAG patients) using a combination of MRW and pRNFL parameters (acquired with the BMO-MRW protocol); the other sample provided a test of how the LDF performed on an independent group (validating set: 34 healthy subjects and 34 POAG patients). The receiver operating curves (ROCs) were plotted for every measurement and contrasted with the proposed LDF. The OCT parameters with the best area under the receiver operating characteristic curve (AUC) were determined. RESULTS: Global MRW and pRNFL thicknesses were significantly thinner in the POAG group (p <  0.001). The BMO-MRW parameters showed good diagnostic accuracy; the largest AUCs reached 0.875 for the LDF and 0.879 for global RNFL thickness using the standard glaucoma application. There were no statistical differences between the AUCs calculated. CONCLUSIONS: BMO-MRW parameters show a strong capability to differentiate between mild glaucoma and control eyes. Our LDF based on the new BMO-MRW OCT protocol did not perform better than isolated parameters.

Changes in peripapillary choroidal thickness in patients with multiple sclerosis.

PURPOSE: To study peripapillary choroidal thickness (PPCT) around the optic disc and establish zones using a new swept source optical coherence tomography (SS-OCT) device. To evaluate PPCT differences between patients with multiple sclerosis (MS) and age- and sex-matched healthy controls. METHODS: A total of 102 healthy subjects and 51 patients with MS were consecutively recruited. Healthy subjects were divided into teaching (n = 51, used to establish choroidal zones) and validating (n = 51, used to compare measurements with MS patients) populations. An optic disc 6.0 × 6.0-mm three-dimensional scan was obtained using SS-OCT Triton. A 26 × 26 cube-grid centred on the optic disc was generated automatically to measure PPCT. Four choroidal zones were established and used to compare PPCT between healthy controls and patients with MS. RESULTS: Peripapillary choroidal thickness (PPCT) was significantly thinner in patients in all concentric zones (p ≤ 0.0001): 134.02 ± 16.59 µm in MS group versus 171.56 ± 12.43 µm in the control group in zone 2; 182.23 ± 20.52 versus 219.03 ± 17.99 µm, respectively, in zone 3; and 223.52 ± 10.70 versus 259.99 ± 10.29 µm, respectively, in zone 4. The choroidal thinning in the MS group tended to decrease as we distanced from the optic nerve head. Peripapillary choroidal thickness (PPCT) had a similar pattern in controls and MS; it was thicker in the superior region, followed by temporal, nasal and inferior regions. CONCLUSION: Patients with MS showed peripapillary choroidal thinning when compared with healthy subjects in all zones around the optic disc. Peripapillary choroidal tissue shows a concentric pattern, increasing in thickness when increasing the distance from the optic nerve. The new SS-OCT could be useful for evaluating choroidal thinning in clinical practice.

Diagnostic ability of inner macular layers to discriminate early glaucomatous eyes using vertical and horizontal B-scan posterior pole protocols.

PURPOSE: To evaluate the diagnostic ability of macular ganglion cell (mGCL) and macular retinal nerve fiber (mRNFL) layers, to detect early glaucomatous eyes, using the new segmentation software of Spectralis optical coherence tomography (OCT) device (Heidelberg Engineering). METHODS: A total of 83 eyes from 83 subjects were included in this observational, prospective cross-sectional study: 43 healthy controls and 40 early primary open-angle glaucoma (POAG) patients. All participants were examined using the Horizontal and Vertical Posterior Pole protocols, and the peripapillary RNFL (pRNFL) protocol of Spectralis OCT device. The new automated retinal segmentation software was applied to horizontal and vertical macular B-scans to determine mGCL and mRNFL thicknesses in each one of the 9 sectors of the Early Treatment Diagnostic Retinopathy Study circle. Thickness of each layer was compared between groups, and the sectors with better area under the receiver operating characteristic curve (AUC) were identified. RESULTS: mGCL was significantly thinner in the POAG group, especially in outer and inner temporal sectors (p<0.001); and mRNFL was significantly thinner in the POAG group in the outer inferior and the outer superior sector (p<0.001). Diagnostic accuracy of inner macular layers was good, and in general mGCL was superior to mRNFL. pRNFL obtained the best diagnostic capability (AUC, 0.886). Horizontal and vertical Posterior Pole protocols performed similarly. CONCLUSIONS: Inner macular layers using either horizontal or vertical B-scans, especially temporal sectors of mGCL, have good diagnostic capability to differentiate early glaucomatous eyes from control eyes; however, pRNFL has the highest diagnostic sensitivity for glaucoma detection.

New Normative Database of Inner Macular Layer Thickness Measured by Spectralis OCT Used as Reference Standard for Glaucoma Detection.

PURPOSE: This study examines the capacity to detect glaucoma of inner macular layer thickness measured by spectral-domain optical coherence tomography (SD-OCT) using a new normative database as the reference standard. METHODS: Participants (N = 148) were recruited from Leuven (Belgium) and Zaragoza (Spain): 74 patients with early/moderate glaucoma and 74 age-matched healthy controls. One eye was randomly selected for a macular scan using the Spectralis SD-OCT. The variables measured with the instrument's segmentation software were: macular nerve fiber layer (mRNFL), ganglion cell layer (GCL), and inner plexiform layer (IPL) volume and thickness along with circumpapillary RNFL thickness (cpRNFL). The new normative database of macular variables was used to define the cutoff of normality as the fifth percentile by age group. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC) of each macular measurement and of cpRNFL were used to distinguish between patients and controls. RESULTS: Overall sensitivity and specificity to detect early-moderate glaucoma were 42.2% and 88.9% for mRNFL, 42.4% and 95.6% for GCL, 42.2% and 94.5% for IPL, and 53% and 94.6% for RNFL, respectively. The best macular variable to discriminate between the two groups of subjects was outer temporal GCL thickness as indicated by an AUROC of 0.903. This variable performed similarly to mean cpRNFL thickness (AUROC = 0.845; P = 0.29). CONCLUSIONS: Using our normative database as reference, the diagnostic power of inner macular layer thickness proved comparable to that of peripapillary RNFL thickness. TRANSLATIONAL RELEVANCE: Spectralis SD-OCT, cpRNFL thickness, and individual macular inner layer thicknesses show comparable diagnostic capacity for glaucoma and RNFL, GCL, and IPL thickness may be useful as an alternative diagnostic test when the measure of cpRNFL shows artifacts.

Comparison of peripapillary choroidal thickness between healthy subjects and patients with Parkinson's disease.

PURPOSE: To study peripapillary choroidal thickness (PPCT) in healthy subjects using swept-source optical coherence tomography (SS-OCT), and to evaluate PPCT differences between Parkinson´s disease (PD) patients, and age- and sex-matched healthy controls. DESIGN: Case-control study. METHODS: 80 healthy subjects and 40 PD patients were consecutively recruited in this single institution study. The healthy subjects were divided into two populations: a teaching population (n = 40, used to establish choroidal zones) and a validating population (n = 40, used to compare measurements with PD patients). An optic disc 6.0×6.0 mm three-dimensional scan was obtained using Deep Range Imaging (DRI) OCT Triton. A 26×26 cube-grid centered on the optic disc was generated to automatically measure choroidal thickness. Five concentric choroidal zones were established and used to compare PPCT between healthy and PD patients. RESULTS: PPCT was significantly thicker in PD patients compared with controls in all four concentric zones evaluated (p≤0.0001). PPCT followed a similar pattern in controls and PD; it was thicker in the temporosuperior region, followed by the superior, temporal, nasal, and inferior regions. CONCLUSION: PD patients presented with an increased PPCT in all zones surrounding the optic disc compared with healthy subjects. The peripapillary choroidal tissue showed a concentric pattern, with the thickness increasing with increasing distance from the optic nerve. SS-OCT could be useful for evaluating choroidal thinning in clinical practice.

Evaluation of Contrast Sensitivity, Chromatic Vision, and Reading Ability in Patients with Primary Open Angle Glaucoma.

Purpose. To compare contrast sensitivity, acquired color vision deficiency, and reading ability in patients with glaucoma at different stages of the disease and to establish correlations between visual field parameters and visual function scores. Methods. This prospective cross-sectional study included 121 glaucoma patients. Subjects with a diagnosis of chronic open angle glaucoma were recruited and classified according to Hodapp-Parrish-Anderson criteria. Patients with severe visual field defects were excluded because they were older, which could bias the interpretation of visual function tests. Contrast sensitivity was measured using the Pelli-Robson Chart and the CSV1000E test. Chromatic vision was evaluated using the Farnsworth-panel D15 and the L'Anthony D15 tests of Vision Color Recorder software. Reading ability was measured using Radner-Vissum test. Results. Contrast sensitivity (with photopic and mesopic luminance with glare) differed significantly between patients with early and moderate visual field defects (p < 0.05). Reading ability scores and results of the chromatic vision tests did not differ significantly between the two groups. Significant and moderate Spearman correlations between visual field indexes and contrast sensitivity tests were detected. Conclusions. Contrast sensitivity was significantly worse in patients with moderate glaucoma compared to those with early-stage glaucoma. Evaluation of visual function in clinical practice provides important information to address a glaucoma patient's vision complaints.

Ganglion cell layer measurements correlate with disease severity in patients with Alzheimer's disease.

PURPOSE: To evaluate the thickness of the 10 retinal layers of patients with Alzheimer's disease (AD) using a new segmentation technology of the Spectralis optical coherence tomography (OCT) and to determine whether the thickness of specific layers predicts neurodegeneration or AD severity. METHODS: Patients with AD (n = 150) and age-matched healthy controls (n = 75) were analysed using the segmentation application prototype to automatically segment all retinal layers in a macular scan. Thicknesses of each layer were compared between patients with AD and controls, and between patients with disease durations of less than or at least 3 years. Associations between retinal layer thicknesses, disease duration and AD severity were evaluated. RESULTS: Patients with AD had reduced thickness in the retinal nerve fibre, ganglion cell, inner plexiform and outer nuclear layers (p < 0.05). The inner retinal layers were more affected in patients with long disease duration. Ganglion cell and retinal nerve fibre layer thicknesses were inversely correlated with AD duration and severity. Ganglion cell and inner plexiform layers thicknesses were predictive of axonal damage. CONCLUSIONS: The segmentation application revealed ganglion cell and retinal layer atrophy in patients with AD compared with controls, especially in the inner layers of patients with long disease duration. Ganglion cell layer reduction was associated with increased axonal damage and may predict greater disease severity.

Analysis of optic disk color changes in Alzheimer's disease: a potential new biomarker.

PURPOSE: In the present study, we evaluated changes in the retinal nerve fiber layer (RNFL) and optic disk color (i.e., the level of paleness as an indirect sign of axonal loss) in patients with Alzheimer's disease (AD) compared with healthy controls. The usefulness of this method as a new biomarker for AD was also evaluated. METHODS: Fifty-six patients with mild or moderate AD and 56 sex-and age-matched healthy subjects were included in this cross-sectional study. All subjects underwent a complete neuro-ophthalmologic examination, including analysis of the RNFL thickness with Cirrus optical coherence tomography (OCT). One photograph of the optic disk was obtained using a Canon CF 60 DSi retinograph, and new colorimetric analysis software (Laguna ONhE) was used to detect color changes in the photographs based on hemoglobin (Hb) values as reference pigment. RESULTS: Mean Hb percentage and Hb content in the outer ring, which corresponds with the neuroretinal rim, calculated by the Laguna ONhE program were significantly lower in AD patients than in healthy controls (P<0.005). OCT measurements revealed that the mean RNFL thickness was significantly decreased in AD patients compared with healthy controls (P<0.003). CONCLUSION: Analysis of the optic disk color assessed by Laguna ONhE software revealed papillary paleness due to axonal loss and perfusion alterations, even in the early stages of AD. Application of this simple method in routine clinical practice may provide a good biomarker of AD.

Artificial neural network techniques to improve the ability of optical coherence tomography to detect optic neuritis.

PURPOSE: To analyze the ability of Spectralis optical coherence tomography (OCT) to detect multiple sclerosis (MS) and to distinguish MS eyes with antecedent optic neuritis (ON). To analyze the capability of artificial neural network (ANN) techniques to improve the diagnostic precision. METHODS: MS patients and controls were enrolled (n = 217). OCT was used to determine the 768 retinal nerve fiber layer thicknesses. Sensitivity and specificity were evaluated to test the ability of OCT to discriminate between MS and healthy eyes, and between MS with and without antecedent ON using ANN. RESULTS: Using ANN technique multilayer perceptrons, OCT could detect MS with a sensitivity of 89.3%, a specificity of 87.6%, and a diagnostic precision of 88.5%. Compared with the OCT-provided parameters, the ANN had a better sensitivity-specificity balance. CONCLUSIONS: ANN technique improves the capability of Spectralis OCT to detect MS disease and to distinguish MS eyes with or without antecedent ON.

Potential new diagnostic tool for Alzheimer's disease using a linear discriminant function for Fourier domain optical coherence tomography.

PURPOSE: We calculated and validated a linear discriminant function (LDF) for Fourier domain optical coherence tomography (OCT) to improve the diagnostic ability of retinal and retinal nerve fiber layer (RNFL) thickness parameters in the detection of Alzheimer's disease (AD). METHODS: We enrolled AD patients (n = 151) and age-matched, healthy subjects (n = 61). The Cirrus and Spectralis OCT systems were used to obtain retinal measurements and circumpapillary RNFL thickness for each participant. An LDF was calculated using all retinal and RNFL OCT measurements. Receiver operating characteristic (ROC) curves were plotted and compared among the LDF and the standard parameters provided by OCT devices. Sensitivity and specificity were used to evaluate diagnostic performance. A validating set was used in an independent population to test the performance of the LDF. RESULTS: The optimal function was calculated using the RNFL thickness provided by Spectralis OCT, using the 768 points registered during peripapillary scan acquisition (grouped to obtain 24 uniformly divided locations): 18.325 + 0.056 × (315°-330°) - 0.122 × (300°-315°) - 0.041 × (285°-300°) + 0.091 × (255°-270°) + 0.041 × (225°-240°) + 0.183 × (195°-210°) - 0.108 × (150°-165°) - 0.092 × (75°-90°) + 0.051 × (30°-45°). The largest area under the ROC curve was 0.967 for the LDF. At 95% fixed specificity, the LDF yielded the highest sensitivity values. CONCLUSIONS: Measurements of RNFL thickness obtained with the Spectralis OCT device differentiated between healthy and AD individuals. Based on the area under the ROC curve, the LDF was a better predictor than any single parameter.

Influence of cataract surgery on repeatability and measurements of spectral domain optical coherence tomography.

BACKGROUNDS/AIMS: To evaluate the effect of uncomplicated cataract phacoemulsification on the measurements of macular and retinal nerve fibre layer (RNFL) in healthy subjects using two spectral domain (SD) optical coherence tomography (OCT) instruments--Cirrus OCT (Zeiss) and Spectralis OCT (Heidelberg)--and to assess the reliability of the measurements obtained with these two devices before and after cataract surgery. METHODS: The study included 60 eyes of 60 healthy subjects (22 men and 38 women, 54-88 years of age) who underwent cataract phacoemulsification. One month before and one month after surgery, three repetitions of scans were performed using the RNFL and macular analysis protocols of the Cirrus and Spectralis OCT instruments. The differences between RNFL and macular thickness measurements obtained in the two visits were analysed. Repeatability was evaluated by calculating the coefficient of variation (COV) for each of the parameters recorded and for each visit. RESULTS: The RNFL measurements obtained with the Cirrus and Spectralis OCT differed before and after surgery, and most of these differences were statistically significant (p<0.05). Macular thickness measurements using the Spectralis OCT were not significantly different between the two visits, whereas the differences found with the Cirrus OCT were statistically significant. The repeatability was better after surgical removal of the cataract, and the differences between COV in the two visits were significant with the Cirrus OCT. CONCLUSIONS: The presence of cataracts affects RNFL and macular measurements performed with SD-OCT. The repeatability of the images significantly improved after cataract phacoemulsification when using the Cirrus OCT.

Electropysiologic evaluation of the visual pathway in patients with multiple sclerosis.

PURPOSE: To evaluate the ability of visual evoked potentials and pattern electroretinograms (PERG) to detect subclinical axonal damage in patients during the early diagnostic stage of multiple sclerosis (MS). The authors also compared the ability of optical coherence tomography (OCT), PERG, and visual evoked potentials to detect axonal loss in MS patients and correlated the functional and structural properties of the retinal nerve fiber layer. METHODS: Two hundred twenty-eight eyes of 114 subjects (57 MS patients and 57 age- and sex-matched healthy controls) were included. The visual pathway was evaluated based on functional and structural assessments. All patients underwent a complete ophthalmic examination that included assessment of visual acuity, ocular motility, intraocular pressure, visual field, papillary morphology, OCT, visual evoked potentials, and PERG. RESULTS: Visual evoked potentials (P100 latency and amplitude), PERG (N95 amplitude and N95/P50 ratio), and OCT parameters differed significantly between MS patients and healthy subjects. Moderate significant correlations were found between visual evoked potentials or PERG parameters and OCT measurements. CONCLUSIONS: Axonal damage in ganglion cells of the visual pathway can be detected based on structural measures provided by OCT in MS patients and by the N95 component and N95/P50 index of PERG, thus providing good correlation between function and structure.

Influence of cataract surgery on optical coherence tomography and neurophysiology measurements in patients with retinitis pigmentosa.

PURPOSE: To evaluate the effect of uncomplicated cataract phacoemulsification on the measurements of visual evoked potentials (VEP), pattern electroretinogram (PERG), and macular and retinal nerve fiber layer (RNFL) using 2 spectral-domain optical coherence tomography (OCT) instruments, the Cirrus OCT (Carl Zeiss Meditech) and Spectralis OCT (Heidelberg Engineering), in patients with retinitis pigmentosa (RP), and to assess the reliability of the OCT measurements before and after cataract surgery. DESIGN: Observational cross-sectional study. METHODS: Thirty-five eyes of 35 patients with RP (20 men and 15 women, 45-66 years) who underwent cataract phacoemulsification were studied. At 1 month before and 1 month after surgery, visual acuity, VEP, PERG, and 3 repetitions of scans using the RNFL and macular analysis protocols of the Cirrus and Spectralis OCT instruments were performed. The differences in measurements between the 2 visits were analyzed. Repeatability of OCT measurements was evaluated by calculating the coefficients of variation. RESULTS: VEP amplitude, RNFL thicknesses provided by Cirrus and Spectralis, and macular measurements provided by Cirrus OCT differed between the 2 visits. VEP latency, PERG measurements, and macular thicknesses provided by the Spectralis OCT before surgery did not differ significantly from those after surgery. The OCT repeatability was better after surgery, with lower coefficients of variation for scans performed after surgical removal of the cataract. The nuclear, cortical, and posterior subcapsular types of cataracts did not show different repeatability. CONCLUSIONS: The presence of cataracts affects VEP amplitude, RNFL, and macular measurements performed with OCT in eyes with RP. Image repeatability significantly improves after cataract phacoemulsification.

Ability and reproducibility of Fourier-domain optical coherence tomography to detect retinal nerve fiber layer atrophy in Parkinson's disease.

PURPOSE: To evaluate and compare the ability of 3 protocols of Fourier-domain optical coherence tomography (OCT) to detect retinal thinning and retinal nerve fiber layer (RNFL) atrophy in patients with Parkinson's disease (PD) compared with healthy subjects. To test the intrasession reproducibility of RNFL thickness measurements in patients with PD and healthy subjects using the Cirrus (Carl Zeiss Meditec Inc., Dublin, CA) and Spectralis (Heidelberg Engineering, Inc., Heidelberg, Germany) OCT devices. DESIGN: Observational, cross-sectional study. PARTICIPANTS: Patients with PD (n = 75) and age-matched healthy subjects (n = 75) were enrolled. METHODS: All subjects underwent three 360-degree circular scans centered on the optic disc by the same experienced examiner using the Cirrus OCT instrument, the classic glaucoma application, and the new Nsite Axonal Analytics of the Spectralis OCT instrument. MAIN OUTCOME MEASURES: Differences between the eyes of healthy subjects and the eyes of patients with PD were compared using the 3 protocols. The relationship between measurements provided by each OCT protocol was evaluated. Repeatability was studied by intraclass correlation coefficients and coefficients of variation. RESULTS: Retinal nerve fiber layer atrophy was detected in eyes of patients with PD (P = 0.025, P=0.042, and P < 0.001) with the 3 protocols used, but the Nsite Axonal Analytics of the Spectralis OCT device was the most sensitive for detecting subclinical defects. In eyes of patients with PD, RNFL thickness measurements determined by the OCT devices were correlated, but they were significantly different between the Cirrus and Spectralis devices (P = 0.038). Reproducibility was good with all 3 protocols but better using the Glaucoma application of the Spectralis OCT device. CONCLUSIONS: Fourier-domain OCT can be considered a valid and reproducible device for detecting subclinical RNFL atrophy in patients with PD, especially the Nsite Axonal Analytics of the Spectralis device. Retinal nerve fiber layer thickness measurements differed significantly between the Cirrus and Spectralis devices despite a high correlation of the measurements between the 2 instruments.