Reproducibility of retinal and choroidal measurements using swept-source optical coherence tomography in patients with Parkinson's disease / Reprodutibilidade das medições da retina e da coroideia utilizando a tomografia de coerência ótica Swept-Source em pacientes com a doença de Parkinson

ABSTRACT Purpose: To assess the reproducibility of retinal and choroidal measurements in the macular and peripapillary areas using swept-source optical coherence tomography in patients with Parkinson's disease. Methods: A total of 63 eyes of 63 patients with idiopathic Parkinson's disease were evaluated using a three-dimensional protocol of swept-source optical coherence tomography. The following layers were analyzed: full retinal thickness, retinal nerve fiber layer, ganglion cell layer, and choroid. The coefficient of variation was calculated for every measurement. Results: In the macular area, the mean coefficients of variation of retinal thickness, ganglion cell layer + thickness, and choroidal thickness were 0.40%, 0.84%, and 2.09%, respectively. Regarding the peripapillary area, the mean coefficient of variation of the retinal nerve fiber layer thickness was 2.78. The inferior quadrant showed the highest reproducibility (coefficient of variation= 1.62%), whereas the superonasal sector showed the lowest reproducibility (coefficient of variation= 8.76%). Conclusions: Swept-source optical coherence tomography provides highly reproducible measurements of retinal and choroidal thickness in both the macular and peripapillary areas. The reproducibility is higher in measurements of retinal thickness versus choroidal thickness.

RESUMO Objetivo: Avaliar a reprodutibilidade das medições da retina e da coroide nas áreas macular e peripapilar utilizando a tomografia de coerência ótica com fonte de varredura pacientes com doença de Parkinson. Métodos: Um total de 63 olhos de 63 pacientes com doença de Parkinson idiopática foram avaliados usando um protocolo 3D de tomografia de coerência ótica de fonte Triton Swept. Foram analisadas as seguintes camadas: espessura retiniana total, camada de fibras nervosas da retina, camada de células ganglionares e coróide. O coeficiente de variação foi calculado para cada medição. Resultados: Na área macular, os coeficientes médios de variação da espessura da retina, da camada de células ganglionares + espessura e da espessura da coróide foram de 0,40%, 0,84% e 2,09%, respectivamente. Em relação à área peripapilar, o coeficiente médio de variação da espessura da camada de fibras nervosas da retina foi de 2,78%. O quadrante inferior apresentou a maior reprodutibilidade (coeficiente de variação= 1,62%), enquanto o setor superonasal apresentou a menor reprodutibilidade (coeficiente de variação= 8,76%). Conclusões: A tomografia de coerência ótica de fonte Triton Swept fornece medições altamente reprodutíveis da espessura da retina e da coroide nas áreas macular e peripapilar. A reprodutibilidade é maior nas medidas da espessura da retina versus a espessura da coróide.

Reproducibility of retinal and choroidal measurements using swept-source optical coherence tomography in patients with Parkinson's disease.

PURPOSE: To assess the reproducibility of retinal and choroidal measurements in the macular and peripapillary areas using swept-source optical coherence tomography in patients with Parkinson's disease. METHODS: A total of 63 eyes of 63 patients with idiopathic Parkinson's disease were evaluated using a three-dimensional protocol of swept-source optical coherence tomography. The following layers were analyzed: full retinal thickness, retinal nerve fiber layer, ganglion cell layer, and choroid. The coefficient of variation was calculated for every measurement. RESULTS: In the macular area, the mean coefficients of variation of retinal thickness, ganglion cell layer + thickness, and choroidal thickness were 0.40%, 0.84%, and 2.09%, respectively. Regarding the peripapillary area, the mean coefficient of variation of the retinal nerve fiber layer thickness was 2.78. The inferior quadrant showed the highest reproducibility (coefficient of variation= 1.62%), whereas the superonasal sector showed the lowest reproducibility (coefficient of variation= 8.76%). CONCLUSIONS: Swept-source optical coherence tomography provides highly reproducible measurements of retinal and choroidal thickness in both the macular and peripapillary areas. The reproducibility is higher in measurements of retinal thickness versus choroidal thickness.

Retinal and Choroidal Changes in Patients with Parkinson's Disease Detected by Swept-Source Optical Coherence Tomography.

PURPOSE: To evaluate the ability of new Swept source (SS) optical coherence tomography (OCT) technology to detect changes in retinal and choroidal thickness in patients with Parkinson's disease (PD). DESIGN: Observational case-control cross sectional study, developed from January to May 2016. METHODS: In total, 50 eyes from 50 patients diagnosed with PD and 54 eyes of 54 healthy controls underwent retinal and choroidal assessment using SS DRI Triton OCT (Topcon), using the 3D Wide protocol. Total macular thickness and peripapillary data (retinal, ganglion cell layer [GCL+, GCL++] and retinal nerve fiber layer [RNFL] thickness) were analyzed. Macular and peripapillary choroidal thickness was evaluated (Figure 1). RESULTS: Significant peripapillary retinal thinning was observed in PD patients in total average (p = 0.017), in the nasal (p = 0.038) and temporal (p = 0.004) quadrants and in superotemporal (p = 0.004), nasal (p = 0.039), inferotemporal (p = 0.019), and temporal (p = 0.003) sectors. RNFL and GCL ++ thickness showed a significant reduction in the inferotemporal sector (p = 0.026 and 0.009, respectively). No differences were observed in macular retinal thickness between controls and patients. Choroidal thickness was found to have increased in all sectors in PD patients compared with controls, both in the macular (inner nasal, p = 0.015; inner inferior, p = 0.030; outer nasal, p = 0.012; outer inferior, p = 0.049) and the peripapillary area (total thickness, p = 0.011; nasal, p = 0.025; inferior, p = 0.007; temporal, p = 0.003; inferotemporal, p = 0.003; inferonasal, p = 0.016) Conclusion: New SS technology for OCT devices detects retinal thinning in PD patients, providing increased depth analysis of the choroid in these patients. The choroid in PD may present increased thickness compared to healthy individuals; however, more studies and histological analysis are needed to corroborate our findings.

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 Progressive Visual Dysfunction and Retinal Degeneration in Patients With Parkinson's Disease.

Purpose: To quantify changes in visual function parameters and in the retinal nerve fiber layer and macular thickness over a 5-year period in patients with Parkinson's disease (PD). Methods: Thirty patients with PD and 30 healthy subjects underwent a complete ophthalmic evaluation, including assessment of visual acuity, contrast sensitivity vision, color vision, and retinal evaluation with spectral-domain optical coherence tomography (SD-OCT). All subjects were reevaluated after 5 years to quantify changes in visual function parameters, the retinal nerve fiber layer, and macular thickness. Association between progressive ophthalmologic changes and disease progression was analyzed. Results: Changes were detected in visual function parameters and retinal nerve fiber layer thickness in patients compared with controls. Greater changes were found during the follow-up in the PD group than healthy subjects in visual acuity, contrast sensitivity, Lanthony color test (P < 0.016), in superotemporal and temporal retinal nerve fiber layer sectors (P < 0.001), and in macular thickness (all sectors except inner superior and inner inferior sectors, P < 0.001). Progressive changes in the retinal nerve fiber layer were associated with disease progression (r = 0.389, P = 0.028). Conclusions: Progressive visual dysfunction, macular thinning, and axonal loss can be detected in PD. Analysis of the macular thickness and the retinal nerve fiber layer by SD-OCT can be useful for evaluating Parkinson's disease progression.

Optical Coherence Tomography as a Biomarker for Diagnosis, Progression, and Prognosis of Neurodegenerative Diseases.

Neurodegenerative diseases present a current challenge for accurate diagnosis and for providing precise prognostic information. Developing imaging biomarkers for multiple sclerosis (MS), Parkinson disease (PD), and Alzheimer's disease (AD) will improve the clinical management of these patients and may be useful for monitoring treatment effectiveness. Recent research using optical coherence tomography (OCT) has demonstrated that parameters provided by this technology may be used as potential biomarkers for MS, PD, and AD. Retinal thinning has been observed in these patients and new segmentation software for the analysis of the different retinal layers may provide accurate information on disease progression and prognosis. In this review we analyze the application of retinal evaluation using OCT technology to provide better understanding of the possible role of the retinal layers thickness as biomarker for the detection of these neurodegenerative pathologies. Current OCT analysis of the retinal nerve fiber layer and, specially, the ganglion cell layer thickness may be considered as a good biomarker for disease diagnosis, severity, and progression.

Electrophysiology and optical coherence tomography to evaluate Parkinson disease severity.

PURPOSE: To evaluate correlations between visual evoked potentials (VEP), pattern electroretinogram (PERG), and macular and retinal nerve fiber layer (RNFL) thickness measured by optical coherence tomography (OCT) and the severity of Parkinson disease (PD). METHODS: Forty-six PD patients and 33 age and sex-matched healthy controls were enrolled, and underwent VEP, PERG, and OCT measurements of macular and RNFL thicknesses, and evaluation of PD severity using the Hoehn and Yahr scale to measure PD symptom progression, the Schwab and England Activities of Daily Living Scale (SE-ADL) to evaluate patient quality of life (QOL), and disease duration. Logistical regression was performed to analyze which measures, if any, could predict PD symptom progression or effect on QOL. RESULTS: Visual functional parameters (best corrected visual acuity, mean deviation of visual field, PERG positive (P) component at 50 ms -P50- and negative (N) component at 95 ms -N95- component amplitude, and PERG P50 component latency) and structural parameters (OCT measurements of RNFL and retinal thickness) were decreased in PD patients compared with healthy controls. OCT measurements were significantly negatively correlated with the Hoehn and Yahr scale, and significantly positively correlated with the SE-ADL scale. Based on logistical regression analysis, fovea thickness provided by OCT equipment predicted PD severity, and QOL and amplitude of the PERG N95 component predicted a lower SE-ADL score. CONCLUSIONS: Patients with greater damage in the RNFL tend to have lower QOL and more severe PD symptoms. Foveal thicknesses and the PERG N95 component provide good biomarkers for predicting QOL and disease severity.

Mitochondrial complex enzyme activities and cytochrome C expression changes in multiple sclerosis.

Blood platelets have been widely proposed as biomarkers in studies of mitochondrial function and aging-related and neurodegenerative diseases. Defects in mitochondrial function were found not only in the substantia nigra of Parkinson's disease patients but also in their blood platelets. Similarly, it has also been described in the blood platelet mitochondria of Alzheimer's disease patients. To study mitochondrial aerobic metabolism function and protein expression in platelets of multiple sclerosis (MS) patients and control subjects, mitochondrial aconitase, mitochondrial superoxide dismutases 1 and 2 (SOD1 and SOD2), and respiratory complex enzyme activities in platelets of MS patients and control subjects were determined. Likewise, mitochondrial lipid peroxidation and mitochondrial SOD1 and cytochrome c expressions were investigated. Mitochondrial aconitase activity was higher in MS patients than in controls (P < 0.05). A significant increase on all respiratory complex activities in MS patients was observed (P < 0.05). Mitochondrial lipid peroxidation was significantly higher in MS patients than in controls (P < 0.05). Significant changes of cytochrome c and mitochondrial SOD1 expressions were detected (P < 0.05), with a decrease of 44 ± 5 % and an increase of 46 ± 6 %, respectively. Our study reveals that significant changes in mitochondrial aerobic metabolism function and mitochondrial SOD1 and cytochrome c expressions are produced in platelets of MS patients.

Distribution of retinal layer atrophy in patients with Parkinson disease and association with disease severity and duration.

PURPOSE: To evaluate the thickness of the 10 retinal layers in the paramacular area of Parkinson disease patients using a new segmentation technology of optical coherence tomography (OCT) to examine whether the thickness of specific layers predicts neurodegeneration or Parkinson disease severity. DESIGN: Observational prospective study. METHODS: Parkinson disease patients (n = 129) and age-matched healthy subjects (n = 129) were enrolled. The Spectralis OCT system was used to automatically segment all retinal layers in a parafoveal scan using the new segmentation application prototype. Mean thickness of each layer was calculated and compared between Parkinson disease patients and healthy subjects, and between Parkinson disease patients with disease durations of less than or at least 10 years. A correlation analysis was performed to evaluate the association between retinal layer thickness, duration of disease, and Parkinson disease severity. Logistic regression analysis was performed to determine the most sensitive layer for predicting axonal atrophy. RESULTS: Parkinson disease patients showed statistically significant reduced thickness in the retinal nerve fiber, ganglion cell, inner plexiform, and outer plexiform layers and increased thickness in the inner nuclear layer compared with healthy subjects (P < .05). The inner retinal layers were more affected in Parkinson disease patients with long disease duration. The ganglion cell layer thickness was inversely correlated with disease duration and Parkinson disease severity, and was predictive of axonal damage in Parkinson disease patients. CONCLUSIONS: The segmentation application of the Spectralis OCT revealed retinal layer atrophy in Parkinson disease patients, especially in the inner layers of patients with long disease duration. Ganglion cell layer reduction was associated with increased axonal damage.

Retina measurements for diagnosis of Parkinson disease.

PURPOSE: To test the diagnostic ability of spectral domain optical coherence tomography for the detection of Parkinson disease using retinal nerve fiber layer and retinal thickness parameters. Retinal pigment epithelium produces levodopa. METHODS: Patients with Parkinson disease (n = 111) and healthy subjects (n = 200) were enrolled. The Spectralis optical coherence tomography was used to obtain retinal nerve fiber layer thickness and retinal measurements. Two linear discriminant functions (LDFs) were developed, one using retinal nerve fiber layer parameters and another using retinal thickness. A validating set was used to test the performance of both LDFs. Receiver operating characteristic curves were plotted and compared with the standard parameters provided by optical coherence tomography for both LDFs. Sensitivity and specificity were used to evaluate diagnostic performance. RESULTS: The Retinal LDF combines only retinal thickness parameters and provided the best performance: 31.173 + 0.026 × temporal outer - 0.267 × superior outer + 0.159 × nasal outer - 0.197 × inferior outer - 0.060 × superior inner + 0.049 × foveal thickness. The largest areas under the receiver operating characteristic curve were 0.902 for Retinal LDF. The Retinal LDF yielded the highest sensitivity values. CONCLUSION: Measurements of retinal thickness differentiate between subjects who are healthy and those with advanced Parkinson disease.

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.

Increased serum interleukin-17 levels in patients with myasthenia gravis.

It has been suggested that interleukin-17 (IL-17) plays a crucial role in the development of several autoimmune diseases. However, there are no data about the relationship between myasthenia gravis and IL-17. The aim of this study was to measure the concentration of IL-17 and determine whether levels depend on the severity of MG. Serum IL-17 concentrations were measured in 25 patients. IL-17 concentrations were higher in generalized MG compared with controls and correlated with anti-acetylcholinesterase receptor antibody titers.