The intrinsically restructured fovea is correlated with contrast sensitivity loss in Parkinson's disease.

Foveal structure that is specified by the thickness, depth and the overall shape of the fovea is a promising tool to qualify and quantify retinal pathology in Parkinson's disease. To determine the model variable that is best suited for discriminating Parkinson's disease eyes from those of healthy controls and to assess correlations between impaired contrast sensitivity and foveal shape we characterized the fovea in 48 Parkinson's disease patients and 45 control subjects by optical coherence tomography (OCT). The model quantifies structural changes in the fovea of Parkinson's disease patients that are correlated with a decline in contrast sensitivity. Retinal foveal remodeling may serve as a parameter for vision deficits in Parkinson's disease. Whether foveal remodeling reflects dopaminergic driven pathology or rather both dopaminergic and non-dopaminergic pathology has to be investigated in longitudinal studies.

A combination of retinal morphology and visual electrophysiology testing increases diagnostic yield in Parkinson's disease.

BACKGROUND: Impaired vision and remodeled foveal pit have been demonstrated in Parkinson's disease (PD) patients using different techniques. METHODS: Ten PD (20 eyes) and eight healthy controls (HC) subjects (16 eyes) were enrolled. Subjects were evaluated for N70 and P100 latencies using two-channel VEP with pattern reversal and on/off pattern; Contrast sensitivity (CS) using Pelli-Robson chart; macular thickness measured using Zeiss-HD optical coherence tomography (OCT). RESULTS: PD patients had a significantly delayed N70 (reversal pattern) and P100 (on/off pattern), lower CS score, and decreased retinal thickness at temporal 1.5-2.5 mm from the foveola. N70 latency was negatively correlated with CS (R = -0.419, P = 0.01) and average GCL-IPL thickness (R = -0.529, P = 0.001). CS was positively correlated with parafoveal thickness (R = 0.490, P = 0.002). A combination of parafoveal thickness and CS score yielded an AUC of 0.784 for PD discrimination which increased to 0.844 when combined with N70 and P100 measures. CONCLUSION: A combination of pattern reversal VEP latency, CS score, and inner retinal foveal thickness measures has a high diagnostic yield for PD.

A novel retinal biomarker for Parkinson's disease: Quantifying the foveal pit with optical coherence tomography.

BACKGROUND: Optical coherence tomography offers a potential biomarker tool in Parkinson's disease (PD). A mathematical model quantifying symmetry, breadth, and depth of the fovea was applied. METHODS: Nintey-six subjects (72 PD and 24 healthy controls) were included in the study. Macular scans of each eye were obtained on two different optical coherence tomography devices: Cirrus and RTVue. RESULTS: The variables corresponding to the cardinal gradients of the fovea were the most sensitive indicators of PD for both devices. Principal component analysis distinguished 65% of PD patients from controls on Cirrus, 57% on RTVue. CONCLUSION: Parkinson's disease shallows the superior/inferior and to a lesser degree nasal-temporal foveal slope. The symmetry, breadth, and depth model fits optical coherence tomography data derived from two different devices, and it is proposed as a diagnostic tool in PD.

Dance for PD: a preliminary investigation of effects on motor function and quality of life among persons with Parkinson's disease (PD).

In 2001, Dance for Parkinson's disease (DfPD(®)) classes for persons with Parkinson's disease and care partners were developed by Brooklyn Parkinson Group and Mark Morris Dance Group. A previous assessment suggested that individuals experience positive benefits from DfPD(®). The current preliminary uncontrolled study investigated the effects of a dance intervention on several motor and quality of life aspects of PD following 16 sessions (8 weeks; 20 h) taught by professional dancers/teachers. A mixed methods design was used to determine the effects of the class. Assessment instruments administered at baseline and post-intervention included the Hoehn and Yahr, UPDRS (part III), Berg Balance Scale, Beck Depression Inventory, and PDQ-39 and individual interviews after the last class. Hoehn and Yahr scores ranged from 1 to 4. UPDRS III total scores and sub scores of gait and tremor improved following the intervention (P < 0.05). During interviews participants reported physical, emotional, and social benefits. Despite the diversity of baseline measures post-class interview results were consistently positive across the sample. Twelve of 14 subjects (mean age 66.2) with idiopathic PD completed the sessions. After 4 years, four participants regularly attended DfPD(®) classes. The low attrition rate and continued attendance suggest notable adherence to the DfPD(®) class. The importance of the results is both clinical and conceptual, highlighting the value of using both quantitative and qualitative data to evaluate the benefits of dance with PD.

The avascular zone and neuronal remodeling of the fovea in Parkinson disease.

Inner foveal thinning and intracellular alpha-synuclein were demonstrated in the retina in Parkinson disease. While pathognomonic alpha-synuclein is associated with embryonic dopaminergic (DA) neurons, postmortem studies in the nervous system and retina show prominent effect also in non-DA neurons. We evaluated foveal capillaries and foveal thickness in 23 Parkinson disease subjects and 13 healthy controls using retinal fluorescein angiography and optical coherence tomography. The size of the foveal avascular zone inversely correlates with foveal thinning. Foveal thinning highly correlates with motor impairment and also disease duration. Quantifying capillary and neuronal remodeling could serve as biological markers.

Activity engagement and health quality of life in people with Parkinson's disease.

PURPOSE: This descriptive study examined differences in health quality of life (HQoL) and activity engagement in two groups of people with Parkinson's disease (PD): those who regularly participated in classes offered by the community-based program, Brooklyn Parkinson's Group (BPg), and a comparison group. Individuals in the comparison group did not participate in any community-based programs for people with PD, and were recruited from a clinic for PD and related disorders (PDRD) in an urban medical center. METHOD: We enrolled 26 participants; 13 participants were recruited from BPg and 13 from PDRD Clinic. Activity engagement was measured using the Activity Card Sort (ACS) and HQoL was measured using the PD Questionnaire (PDQ-39). Additionally, each participant completed a brief, interview-based questionnaire. RESULTS: A statistically significant difference was found in ACS scores between the BPg and comparison groups. BPg participants showed higher activity retention scores in all domains measured by the ACS. There was no statistically significant difference in PDQ-39 scores. CONCLUSION: This study provides preliminary evidence that regular participation in community programs like BPg may increase retention rates of activity engagement in people with PD. Participation in BPg programs, though, was not shown to improve HQoL as measured by the PDQ-39. Implications for Rehabilitation Continued participation in a wide repertoire of activities is a valuable rehabilitation goal for clients with Parkinson's disease (PD). People with PD who participate in specially designed community-based programs are more likely to retain a wide repertoire of activity and role engagement, as compared to people with PD who do not have acess to these programs.

α-synuclein in the inner retina in parkinson disease.

Behavioral, electrophysiological, and imaging data reveal impaired visual processing and altered retinal morphology in Parkinson disease. Are visual changes epiphenomena? We report the presence of misfolded α-synuclein in the retina, not hitherto shown, in discrete retinal neurons within the inner retina. They demonstrate the histopathology that may underlie impaired vision and retinal remodeling in Parkinson disease. Furthermore, the histological localization of α-synuclein gives clues to the nonsynaptic mode of α-synuclein propagation.

Application of an OCT data-based mathematical model of the foveal pit in Parkinson disease.

Spectral-domain Optical coherence tomography (OCT) has shown remarkable utility in the study of retinal disease and has helped to characterize the fovea in Parkinson disease (PD) patients. We developed a detailed mathematical model based on raw OCT data to allow differentiation of foveae of PD patients from healthy controls. Of the various models we tested, a difference of a Gaussian and a polynomial was found to have "the best fit". Decision was based on mathematical evaluation of the fit of the model to the data of 45 control eyes versus 50 PD eyes. We compared the model parameters in the two groups using receiver-operating characteristics (ROC). A single parameter discriminated 70 % of PD eyes from controls, while using seven of the eight parameters of the model allowed 76 % to be discriminated. The future clinical utility of mathematical modeling in study of diffuse neurodegenerative conditions that also affect the fovea is discussed.

Venturing into the no-man's land of the retina in Parkinson's disease.

The development of optical coherence tomography (OCT) has led to increasing interest in the retina in Parkinson's disease (PD). The retina is a multilayered tissue: looking into the eye from the outside, these layers comprise the nerve fiber layer (NFL); the ganglion cell layer (GCL); the inner plexiform layer (IPL), which contains the interconnecting plexus, including tyrosine hydroxylase-positive (dopaminergic) fibers of amacrine cells; the inner nuclear layer; and several outer retinal layers. Commercial spectral-domain OCT has a specific program for detecting peripapillary NFL defects and a different macular program for diabetic retinopathy. Specific programs for PD are not commercially available. Taking all studies together, it seems that macular programs have a higher diagnostic yield than NFL programs, but the numbers of studies and examined patients are relatively small. It is not certain that all retinal thinning in PD is due to dopaminergic neuronal loss. When applying OCT, the where (region of interest) and the what of the focus of automated programs must be considered. With these caveats, one could take advantage of the power of OCT for looking in-depth into the terra incognita of individual retinal layers at the fovea and perhaps at other appropriate retinal locations.

Correlation of inner retinal thickness evaluated by spectral-domain optical coherence tomography and contrast sensitivity in Parkinson disease.

BACKGROUND: To compare inner retinal layer (IRL) thickness measured by spectral-domain optical coherence tomography (SD-OCT) and contrast sensitivity (CS) in patients with Parkinson disease (PD) and in healthy control (HC) subjects. METHODS: Consecutive patients with and without PD were prospectively analyzed using SD-OCT and Pelli-Robson CS testing. SD-OCT IRL (ganglion-cell complex) thickness, consisting of the nerve fiber layer, ganglion cell layer, and inner plexiform layer, was segmented using an RTVue Model-RT100 with an EMM5 scan parameter covering a 5.0 × 5.0 mm cube centered on the fovea. Thickness voxel measurements at 0.25-mm intervals at sequential radial distances from the foveola were acquired horizontally and vertically. SD-OCT thickness raw data files were imported and analyzed within MATLAB (version 7.10.0). A database of CS scores and IRL thickness values by foveal location was constructed and statistically evaluated using JMP 10 (SAS Institute, Inc, Cary, NC). RESULTS: The results were compared between 28 eyes of 14 patients with PD and 28 eyes of 14 HC subjects. Controlling for age, mean CS scores of monocular right and randomized eyes were statistically lower in PD eyes (P < 0.05). IRL was significantly thinner in PD eyes than in HC eyes at several distances from the foveola (P < 0.05). The most numerous and significant thickness differences by diagnosis were located in the superior quadrant at a distance of 1.00-1.75 mm from the foveal center (17 µm; P < 0.01, maximum significant thickness difference and P value). Correlation was demonstrated between monocular CS and IRL thickness by diagnosis at multiple foveal locations for HC eyes as follows: nasal quadrant, 0.75-1.00 mm (P < 0.02); temporal quadrant, 0.50-1.00 mm (P < 0.05); superior quadrant, 1.00 mm (P < 0.05); and inferior quadrant, 1.00 mm (P < 0.03). No significant correlation was found between monocular CS and IRL thickness within PD subjects (P > 0.05 for each foveal location measured). CONCLUSION: CS and foveal IRL thickness are decreased in patients with PD. CS and IRL thickness correlated in HC subjects; however, no such correlation was demonstrated in PD. The functional deficit of dopaminergic interneurons, including amacrine cells, may outstrip the anatomic structural changes in the inner retina of PD patients. Inner retinal atrophic changes may underlie the pathogenesis of CS deficit and IRL thinning in PD.

Fovea and foveation in Parkinson's disease.

Nondemented Parkinson's disease (PD) patients report problems on nonmotor tasks that depend on visual or visuospatial abilities. In PD, foveal vision is impaired. Experimental studies in humans and monkeys established that foveal processing and visuospatial attention may be linked through saccadic eye movements. Saccadic eye movements "bring" eccentric targets to the direct sight line for closer scrutiny by foveal processing. This is called foveation. This review musters the arguments for impaired foveal vision and impaired cortical control of voluntary saccades in PD. Retinal impairment of spatial contrast vision is selective in PD. Thus, the reviewed literature includes a brief survey of the physiology of foveal pathways. This is necessary to understand the specificity of the retinopathy of PD, documented by clinical evidence, relying on psychophysical, electrophysiological, and imaging techniques. These have recently been supplanted by the results of retinal imaging using Optical Coherence Tomography (OCT). Studies of cortical mechanisms in PD reviewed here relied on neuropsychological, electrophysiological (EEG), and imaging techniques. Impaired functional anatomy and electrophysiology in PD are reviewed. The exact relationship of retinal foveal deficits and visuospatial attention and postural control impairment in PD remain challenging research questions. This review will hopefully will provide useful material for future studies.

Interocular asymmetry of foveal thickness in Parkinson disease.

Purpose. To quantify interocular asymmetry (IA) of foveal thickness in Parkinson disease (PD) versus that of controls. Design. Prospective case-control series. Methods. In vivo assessment of foveal thickness of 46 eyes of 23 PD patients and 36 eyes of 18 control subjects was studied using spectral domain optical coherence tomography (SD-OCT). Inner versus outer layer retinal segmentation and macular volumes were quantified using the manufacturer's software, while foveal thickness was measured using the raw data from each eye in a grid covering a 6 by 6 mm area centered on the foveola in 0.25 mm steps. Thickness data were entered into MATLAB software. Results. Macular volumes differed significantly at the largest (Zone 3) diameter centered on the foveola (ETDRS protocol). By segmenting inner from outer layers, we found that the IA in PD is mostly due to changes on the slope of the foveal pit at the radial distances of 0.5 and 0.75 mm (1.5 mm and 1 mm diameter). Conclusions. About half of the PD patients had IA of the slope of the foveal pit. IA is a potentially useful marker of PD and is expected to be comparable across different SD-OCT equipment. Data of larger groups may be developed in future multicenter studies.

Inner retinal layer thinning in Parkinson disease.

OBJECTIVE: To quantify retinal thickness in patients with Parkinson disease (PD). METHODS: Forty-five eyes of 24 PD patients and 31 eyes of 17 control subjects underwent a comprehensive ophthalmologic examination. We used optical coherence tomography to examine retinal thickness, separately quantifying the inner and outer retinal layers. Intraocular pressure was measured by Goldmann applanation tonometry. RESULTS: The mean (SD) ages of the patients with PD and healthy subjects were 64.0 (6.5) years vs 63.5 (10.7) years (P = .77). The mean (SD) intraocular pressure was 13.6 (+/-2.7) mm Hg in the PD patients. No difference was found in either the superior or inferior outer retinal layer thickness of PD vs control eyes. The mean (SD) superior inner retinal layer thickness of PD vs control eyes was 88.79 (11.3) microm vs 103.5 (24.3) microm (P = .01), and the mean inferior inner retinal layer thickness was 89.83 (11.1) microm vs 104.0 (23.5) microm (P = .01). CONCLUSIONS: The inner retinal layer is significantly thinner in PD patients than in healthy subjects. Idiopathic PD, distinct from glaucoma, needs to be considered in the differential diagnosis of retinal nerve fiber layer thinning.

Cortical functional anatomy of voluntary saccades in Parkinson disease.

In Parkinson Disease (PD) several aspects of saccades are affected. The saccade-generating brainstem neurons are spared, however, the signals they receive may be flawed. In particular voluntary saccades suffer, but the functional anatomy of the impairment of saccade-related cortical control is unknown. We measured blood-oxygenation-level-dependent (BOLD) activation with functional Magnetic Resonance Imaging (fMRI) while healthy participants and patients with PD performed horizontal voluntary saccades between peripheral visual targets or fixated centrally. We compared saccade-related BOLD-activity vs. fixation in patients with PD and in healthy controls and correlated perisaccadic BOLD-activity in PD patients with saccade kinetics (multistep saccades). Saccade related BOLD-activation was found in both PD and healthy participants in the superior parietal cortex (PEF) and the occipital cortex. Our results suggest remarkable hypoactivity of the frontal and supplementary eye fields (FEF and SEF) in PD patients. On the other hand, PD patients showed a statistically more reliable BOLD modulation than healthy participants in the posterior cingulate gyrus, the parahippocampal gyrus, inferior parietal lobule, precuneus and in the middle temporal gyrus. Given abnormal frontal and normal PEF responses, our results suggest that in PD a frontal cortical circuitry, known to be associated with saccade planning, selection, and predicting a metric error of the saccade, is deficient.