Maria P. Bambo

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 Parkinsons 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.

Retinal thinning and correlation with functional disability in patients with Parkinson's disease

Aims To determine whether there is an association between retinal thinning and functional rating scales in patients with Parkinsons disease (PD). Materials and methods Patients with PD (n=153) and controls (n=242) underwent evaluations of the macula and retinal nerve fibre layer (RNFL) using two new-generation Fourier domain optical coherence tomography (OCT) devices (Cirrus, Carl Zeiss Meditec, Dublin, California, USA; Spectralis, Heidelberg Engineering, Heidelberg, Germany). PD severity was assessed using the Schwab-England Activities of Daily Living scale, the Unified Parkinson Disease Rating Scale, the Hoehn and Yahr (HY) scale. Retinal and RNFL thicknesses were compared between patients and controls. Correlations between structural parameters and the scores of the neurologic scales were evaluated. Results RNFL parameters were significantly reduced in patients with PD, especially when using the Spectralis OCT device. All macular parameters, except for foveal thickness, differed significantly between controls and patients with PD (p<0.001). HY scores were significantly and inversely correlated with all macular parameters when measured with the Spectralis OCT device (p<0.05) and with RNFL thickness when measured with the Cirrus OCT device (nasal quadrant, sectors 2 and 5). Conclusions The neurodegeneration caused by PD can be detected using Fourier domain OCT. RNFL and macular thicknesses correlate with PD severity.

Use of Fourier-domain OCT to detect retinal nerve fiber layer degeneration in Parkinson’s disease patients

PurposeTo demonstrate axonal loss in the retinal nerve fiber layer (RNFL) of patients with Parkinson’s disease (PD) and to evaluate the ability of Fourier-domain optical coherence tomography (OCT) to detect RNFL degeneration and retinal thinning in these patients.MethodsPD patients (n=100) and healthy subjects (n=100) were included in the study and underwent visual acuity, color vision, and OCT examinations using two next-generation Fourier-domain devices (Spectralis and Cirrus). Differences in the RNFL thicknesses were compared between patients and controls.ResultsRNFL thicknesses were significantly reduced in PD patients compared with healthy subjects, especially those obtained using the Spectralis OCT, in the inferotemporal quadrant (155.6±16.5 μm in healthy eyes vs 142.1±24.9 μm in patients, P=0.040) and in the superotemporal quadrant (142.6±20.9 μm in healthy eyes vs 132.77±18.6 μm in PD patients, P=0.046). Significant differences were observed between controls and patients in relation to mean macular thickness (P=0.031), foveal thickness (P=0.030), and inferior outer thickness (P=0.019).ConclusionPD is associated with RNFL loss and retinal thinning, which is detectable by Fourier-domain OCT measurements.

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 Alzheimers 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.

Reliability and validity of Cirrus and Spectralis optical coherence tomography for detecting retinal atrophy in Alzheimer’s disease

BackgroundTo evaluate and compare the ability of two Fourier-domain optical coherence tomography (OCT) devices to detect retinal and retinal nerve fibre layer (RNFL) atrophy in patients with Alzheimer’s disease (AD) compared with healthy subjects; to test the intra-session reliability of two OCT devices in AD patients and healthy subjects.MethodsAD patients (n=75) and age-matched healthy subjects (n=75) underwent three Macular Cube 200 × 200 protocols using the Cirrus and Spectralis OCT devices and three 360° circular scans centred on the optic disc using the Cirrus OCT device, the classic glaucoma application, and the new Nsite Axonal Analytics application of the Spectralis OCT instrument. Differences between healthy and AD eyes were compared, and measurements provided by each OCT protocol were compared. Reliability was measured using intraclass correlation coefficients and coefficients of variation. Correlations between OCT measurements and disease duration and severity were also analysed.ResultsRetinal thinning was observed in AD eyes in all areas except the fovea using both OCT devices. RNFL atrophy was detected in AD eyes with all three protocols, but the Nsite Axonal application was the most sensitive. Measurements by the two OCT devices were correlated, but differed significantly. Reliability was good using all protocols, but better with the glaucoma application of Spectralis. Mean RNFL thickness provided by the Nsite Axonal application correlated with disease duration.ConclusionsFourier-domain OCT is a valid and reliable technique for detecting subclinical RNFL and retinal atrophy in AD, especially using the Nsite Axonal application. RNFL thickness decreased with disease duration.

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

To evaluate the thickness of the 10 retinal layers of patients with Alzheimers 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.

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.

Detection of retinal nerve fiber layer degeneration in patients with Alzheimer's disease using optical coherence tomography: searching new biomarkers

Editor, A t the present time, researchers are searching for biomarkers and tools to detect the Alzheimer’s disease (AD) in early phases, especially in high-risk families, and to monitor disease progression. Recent studies have revealed degenerative changes in optic nerve fibers, causing thinning of the retinal nerve fiber layer (RNFL) in patients with AD (Berisha et al. 2007; Kirbas et al. 2013). The RNFL comprises axons originating in retinal ganglion cells and can be measured using ocular imaging technologies such as optical coherence tomography (OCT), which provides non-invasive, rapid, objective and reproducible measurements. Retrograde loss of nerve fibers in the retina and optic nerve may be an early biomarker of neurodegeneration in AD, even prior to hippocampal damage, which impacts memory (Valenti 2007). Following this trend, we conducted a study in which we compared RNFL thickness in healthy and AD subjects using the two most commonly available spectral-domain (SD)-OCT machines [Cirrus OCT (Carl Zeiss Meditec, Inc., Dublin, Ireland) and Spectralis OCT (Heidelberg Engineering, Inc., Carlsbad, CA, USA)]. To carry out this prospective, crosssectional study, 57 patients with mild or moderate AD and 57 healthy, age-matched control subjects were included. Inclusion criteria were: confirmed AD diagnosis; best-corrected visual acuity (BCVA) of 0.1 or higher; and intra-ocular pressure <21 mmHg. Exclusion criteria were: presence of significant refractive errors (>5 dioptres of spherical equivalent refraction or three dioptres of astigmatism); systemic conditions that could affect the visual system and history of ocular trauma or concomitant ocular diseases. Each eye was considered separately; one eye from each subject was randomly selected to be included in the analyses, except when one of the eyes was excluded (due to the presence of significant media opacity). All subjects underwent visual acuity, colour vision and OCT examinations using two SDOCT devices. One hundred and fourteen eyes were evaluated: 57 eyes from patients with AD and 57 eyes from healthy subjects. To establish this cohort, we examined 65 patients with AD, but eight patients were not included in the study for the presence of unknown eye disease (two cases) or their inability to perform the full exploration protocol due to their functional status (six cases). Mean age was 75.29 8.64 years in the AD group and 74.77 9.24 years in the control group. Mean disease duration was 3.71 years (range, 1.46– 5.96 years). Age, sex and intra-ocular pressure did not differ significantly between healthy controls and patients with AD (p > 0.05). RNFL thickness measured with the two OCT devices is shown in Table 1. Cirrus OCT revealed significant RNFL thinning in patients

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 Alzheimers 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.

Visual dysfunction and its correlation with retinal changes in patients with Parkinson's disease: an observational cross-sectional study.

Objectives To evaluate visual dysfunction and its correlation with structural changes in the retina in patients with Parkinsons disease (PD). Methods Patients with PD (n=37) and controls (n=37) were included in an observational cross-sectional study, and underwent visual acuity (VA), colour vision (using the Farnsworth and Lanthony desaturated D15 colour tests) and contrast sensitivity vision (CSV; using the Pelli-Robson chart and CSV 1000E test) evaluation to measure visual dysfunction. Structural measurements of the retinal nerve fibre layer (RNFL), and macular and ganglion cell layer (GCL) thicknesses, were obtained using spectral domain optical coherence tomography (SD-OCT). Comparison of obtained data, and correlation analysis between functional and structural results were performed. Results VA (in all different contrast levels) and all CSV spatial frequencies were significantly worse in patients with PD than in controls. Colour vision was significantly affected based on the Lanthony colour test. Significant GCL loss was observed in the minimum GCL+inner plexiform layer. A clear tendency towards a reduction in several macular sectors (central, outer inferior, outer temporal and superior (inner and outer)) and in the temporal quadrant of the RNFL thickness was observed, although the difference was not significant. CSV was the functional parameter most strongly correlated with structural measurements in PD. Colour vision was associated with most GCL measurements. Macular thickness was strongly correlated with macular volume and functional parameters (r>0.70, p<0.05). Conclusions Patients with PD had visual dysfunction that correlated with structural changes evaluated by SD-OCT. GCL measurements may be reliable indicators of visual impairment in patients with PD.