Visual Dysfunction of the Superior Colliculus in De Novo Parkinsonian Patients.

OBJECTIVE: The dual hit hypothesis about the pathogenesis of Parkinson disease (PD) suggests that the brainstem is a convergent area for the propagation of pathological α-synuclein from the periphery to the brain. Although brainstem structures are likely to be affected early in the course of the disease, detailed information regarding specific brainstem regions is lacking. The aim of our study was to investigate the function of the superior colliculus, a sensorimotor brainstem structure, in de novo PD patients compared to controls using brain functional magnetic imaging and visual stimulation paradigms. METHODS: De novo PD patients and controls were recruited. PD subjects were imaged before and after starting PD medications. A recently developed functional magnetic resonance imaging protocol was used to stimulate and visualize the superior colliculus and 2 other visual structures: the lateral geniculate nucleus and the primary visual cortex. RESULTS: In the 22 PD patients, there was no modulation of the superior colliculus responses to the luminance contrasts compared to controls. This implies a hypersensitivity to low luminance contrast and abnormal rapid blood oxygenation level-dependent signal saturation to high luminance contrasts. The lateral geniculate nucleus was only modulated by 3 to 9% luminance contrasts compared to controls. No major differences were found in the primary visual cortex between both groups. INTERPRETATION: Our findings suggest that pathological superior colliculus visual responses in de novo PD patients are present early in the course of the disease. Changes in imaging the superior colliculus could play an important role as a preclinical biomarker of the disease. ANN NEUROL 2020;87:533-546.

Choroidal blood flow after the first intravitreal ranibizumab injection in neovascular age-related macular degeneration patients.

PURPOSE: To analyse choroidal blood flow (ChBF) changes after the first intravitreal ranibizumab injection in naïve, age-related macular degeneration (ARMD) patients. METHODS: Subfoveal ChBF was assessed by laser Doppler flowmetry (LDF) in newly diagnosed ARMD patients. Both treated and untreated eyes were assessed in each subject at each visit before the first intravitreal ranibizumab injection as well as 24 hr (day 1) and 7 days after (day 7). Central macular thickness (CMT), best-corrected visual acuity (BVCA), systemic haemodynamic parameters and LDF parameters were evaluated at each visit. Nonparametric tests were used to compare data between visits and between treated and untreated eyes. RESULTS: Seventeen ARMD patients were included (12 women and five men, 78 ± 8 years old). At day 7 postintravitreal ranibizumab injection, the normalized choroidal blood velocity (ChBVel) change in the treated eye group was significant (-10.2%; p = 0.006). The choroidal blood volume (ChBVol) did not change significantly after intravitreal injection of ranibizumab. There was a trend for a reduction in ChBF at day 7 (-9.1%, p = 0.08). The sensitivity of the experiment was 12% for ChBVel, 16% for ChBVol and 9% for ChBF. CONCLUSION: In conclusion, the laser Doppler technique provides feasible and noninvasive measurements of blood flow parameters before and after intravitreal injection of antivascular endothelial growth factor (anti-VEGF) in patients with exudative ARMD. Choroidal blood velocity decreased as early as 7 days after intravitreal ranibizumab injection, suggesting a vasoconstriction effect of anti-VEGF in large choroidal vessels in front of choriocapillaris (the site of LDF measurement).

Age-related macular degeneration changes the processing of visual scenes in the brain.

In age-related macular degeneration (AMD), the processing of fine details in a visual scene, based on a high spatial frequency processing, is impaired, while the processing of global shapes, based on a low spatial frequency processing, is relatively well preserved. The present fMRI study aimed to investigate the residual abilities and functional brain changes of spatial frequency processing in visual scenes in AMD patients. AMD patients and normally sighted elderly participants performed a categorization task using large black and white photographs of scenes (indoors vs. outdoors) filtered in low and high spatial frequencies, and nonfiltered. The study also explored the effect of luminance contrast on the processing of high spatial frequencies. The contrast across scenes was either unmodified or equalized using a root-mean-square contrast normalization in order to increase contrast in high-pass filtered scenes. Performance was lower for high-pass filtered scenes than for low-pass and nonfiltered scenes, for both AMD patients and controls. The deficit for processing high spatial frequencies was more pronounced in AMD patients than in controls and was associated with lower activity for patients than controls not only in the occipital areas dedicated to central and peripheral visual fields but also in a distant cerebral region specialized for scene perception, the parahippocampal place area. Increasing the contrast improved the processing of high spatial frequency content and spurred activation of the occipital cortex for AMD patients. These findings may lead to new perspectives for rehabilitation procedures for AMD patients.

Scene perception in age-related macular degeneration: Effect of spatial frequencies and contrast in residual vision.

Age-related macular degeneration (AMD) is characterized by a central vision loss. Here, we investigated the ability of AMD patients to process the spatial frequency content of scenes in their residual vision, depending of the luminance contrast level. AMD patients and normally-sighted elderly participants (controls) performed a categorization task involving large scenes (outdoors vs. indoors) filtered in low spatial frequencies (LSF), high spatial frequencies (HSF), and non-filtered scenes (NF). Luminance contrast of scenes was equalized between stimuli using a root-mean square (RMS) contrast normalization. In Experiment 1, we applied an RMS contrast of 0.1 (for luminance values between 0 and 1), a value situated between the mean contrast of LSF and HSF scenes in natural conditions. In Experiment 2, we applied an RMS contrast of 0.3, corresponding to the mean contrast of HSF scenes in natural conditions. In Experiment 3, we manipulated four levels of linearly-increasing RMS contrasts (0.05, 0.10, 0.15, and 0.20) for HSF scenes only. Compared to controls, AMD patients gave more non-responses in the categorization of HSF than NF or LSF scenes, irrespective of the contrast level of scenes. Performances improved as contrast increased in HSF scenes. Controls were not differentially affected by the spatial frequency content of scenes. Overall, results suggest that LSF processing is well preserved in AMD patients and allows efficient scene categorization in their parafoveal residual vision. The HSF processing deficit could be partially restored by enhancing luminance contrast.

PERSISTENT PLACOID MACULOPATHY IMAGED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To describe the case of a patient presenting with persistent placoid maculopathy imaged with optical coherence tomography angiography. METHODS: Case report of a 72-year-old man who presented with blurred vision in his right eye. fundus photography, fluorescein angiography, infracyanine green angiography, fundus autofluorescence imaging, spectral domain optical coherence tomography, optical coherence tomography angiography, and split spectrum amplitude decorrelation angiography were performed. The diagnosis was made based on ophthalmological manifestations and multimodal imaging. RESULTS: The spectral domain optical coherence tomography image of the right eye revealed disruption of the ellipsoid layers, and an underlying sliver of hyporeflectance. In the left eye, there were no obvious changes on spectral domain optical coherence tomography. In both eyes, infracyanine green angiography showed hypocyanescence of the lesions, persisting throughout late phases. In optical coherence tomography angiography, imaging of the choroidal capillary layers revealed hyposignal lesions, topographically corresponding exactly to hypocyanescent lesions on infracyanine green angiography. CONCLUSION: In this patient, a distinct hyposignal on optical coherence tomography angiography, combined with hypocyanescence on infracyanine green angiography, was interpreted as indicating focal hypoperfusion of the choriocapillaris.

Residual abilities in age-related macular degeneration to process spatial frequencies during natural scene categorization.

Age-related macular degeneration (AMD) is characterized by a central vision loss. We explored the relationship between the retinal lesions in AMD patients and the processing of spatial frequencies in natural scene categorization. Since the lesion on the retina is central, we expected preservation of low spatial frequency (LSF) processing and the impairment of high spatial frequency (HSF) processing. We conducted two experiments that differed in the set of scene stimuli used and their exposure duration. Twelve AMD patients and 12 healthy age-matched participants in Experiment 1 and 10 different AMD patients and 10 healthy age-matched participants in Experiment 2 performed categorization tasks of natural scenes (Indoors vs. Outdoors) filtered in LSF and HSF. Experiment 1 revealed that AMD patients made more no-responses to categorize HSF than LSF scenes, irrespective of the scene category. In addition, AMD patients had longer reaction times to categorize HSF than LSF scenes only for indoors. Healthy participants' performance was not differentially affected by spatial frequency content of the scenes. In Experiment 2, AMD patients demonstrated the same pattern of errors as in Experiment 1. Furthermore, AMD patients had longer reaction times to categorize HSF than LSF scenes, irrespective of the scene category. Again, spatial frequency processing was equivalent for healthy participants. The present findings point to a specific deficit in the processing of HSF information contained in photographs of natural scenes in AMD patients. The processing of LSF information is relatively preserved. Moreover, the fact that the deficit is more important when categorizing HSF indoors, may lead to new perspectives for rehabilitation procedures in AMD.

Expression of VEGF and angiopoietins in subfoveal membranes from patients with age-related macular degeneration.

PURPOSE: Vascular endothelial growth factor (VEGF) and angiopoietins are key regulators of angiogenesis. The purpose of this study was to measure mRNA levels of these factors and of their receptors in surgically excised subfoveal membranes from patients with age-related macular degeneration (AMD) and to evaluate their relevance as prognostic markers of postsurgical recurrence of choroidal neovascularization (CNV). DESIGN: Prospective observational case series. METHODS: setting: Institutional. study population: In a prospective series of 24 patients (aged 51 to 91 years) with classic CNV of AMD diagnosed less than 6 months previously, 24 subfoveal membranes (one eye per patient) were surgically removed and collected. Thirteen patients underwent treatment for recurrence of CNV within 6 months of surgery. main outcome measures: Four 8-mu sections were prepared from each membrane for immunohistochemical determination of vascular density (CD31 immunostaining). The remaining tissue was used for preparation of total RNA. The levels of VEGF-A, VEGF-R1, VEGF-R2, neuropilin-1, angiopoietin-1, angiopoietin-2, Tie-2, and hypoxanthine phosphoribosyltransferase mRNAs were determined by real-time reverse-transcriptase polymerase chain reaction. RESULTS: Vascular endothelial growth factor, angiopoietin-1, and angiopoietin-2 appeared to be expressed to variable levels in most samples, whereas Tie-2, VEGF-R1, and VEGF-R2 were undetectable. Low levels of VEGF expression correlated with postsurgical recurrence of CNV (P = .07). Angiopoietin-1 and angiopoietin-2 levels did not predict recurrence (P > .1). CONCLUSION: The results indicate that at the time of surgical excision, subfoveal membranes express angiopoietin-1, VEGF, and, to a lesser degree, angiopoietin-2. Because CNV appears to recur less often in membranes expressing high levels of VEGF, we hypothesize that VEGF acts as a stabilizer of neovessels at this stage of the disease.