Sofya Glazman

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.

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. ANN NEUROL 2014;75:964–966

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 &mgr;m; 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.

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 manufacturers 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.

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.

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 Parkinsons 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.

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.

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

Optical coherence tomography offers a potential biomarker tool in Parkinsons disease (PD). A mathematical model quantifying symmetry, breadth, and depth of the fovea was applied.

Cortical control of saccades in Parkinson disease and essential tremor

A number of studies suggest that some features of essential tremor (ET) and Parkinson disease (PD) overlap. Besides tremor, also some cognitive features have been implicated in ET and PD. There is recent evidence that a common genetic mutation occurs in ET and PD. Saccadic eye movements could provide an easily quantifiable procedure to help in the differential diagnosis in early PD and ET. Being able to distinguish early on the two diseases may help in tailoring therapy. Cortical control of saccades and antisaccades as they pertain to the potential discrimination of PD and ET is reviewed. Imaging and electrophysiological studies are highlighted; however, there are still few studies. Hopefully this review will stimulate further research, in particular in the direction of differences and similarities in the neural circuits involved in PD and ET.

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

Abstract 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.