Silent Brain Infarctions and Leukoaraiosis in Patients With Retinal Ischemia: A Prospective Single-Center Observational Study.

BACKGROUND AND PURPOSE: We aimed to determine the incidence of co-occurring cerebral ischemia, extent of cerebral small vessel disease, and vascular risk profile of patients with acute retinal ischemia. METHODS: RETIS (Frequency of Acute Silent Brain Infarction and Systematic Evaluation of Stroke Risk in Retinal Ischemia) was a single-center, prospective, observational study comprising ophthalmologic examination, brain magnetic resonance imaging, and extensive diagnostic work-up of vascular risk factors and stroke cause. Silent brain infarctions were identified on diffusion-weighted imaging, leukoaraiosis was quantified on fluid-attenuated inversion recovery sequences, and carotid artery stenosis was assessed by carotid ultrasound. RESULTS: Of 112 patients with retinal ischemia, 77 (68.8%) had retinal arterial occlusion, and 35 (31.3%) presented with amaurosis fugax. Silent brain infarctions were found in 17 (15.1%) patients. Internal carotid artery stenosis was present in 19 (17.0%) and severe leukoaraiosis in 29 (25.9%) patients. Atrial fibrillation was detected in 14 (12.5%) patients. Patients with silent brain infarctions had higher rates of internal carotid artery stenosis (35.3% versus 13.7%; P=0.029) than those without, whereas leukoaraiosis and vascular risk factors were comparable between groups. Internal carotid artery stenosis was the only significant predictor of silent brain infarctions in multivariate analysis (odds ratio, 4.27; 95% confidence interval, 1.06-17.23). CONCLUSIONS: Silent cerebral ischemia is present in about 1 in 7 patients with retinal ischemia. The high rate of symptomatic internal carotid artery stenosis suggests that large artery atherosclerosis plays a major role in the pathogenesis of acute retinal ischemia.

A randomized, double-blind, phase 2 study of erythropoietin in optic neuritis.

OBJECTIVE: Based on findings in animal models of autoimmune optic nerve inflammation, we have assessed the safety and efficacy of erythropoietin in patients presenting with a first episode of optic neuritis. METHODS: Patients with optic neuritis who attended the University Hospitals of Homburg/Saar, Göttingen, or Hamburg (Germany) were included in this double-blind, placebo-controlled, phase 2 study (ClinicalTrials.gov, NCT00355095). They were randomly assigned to groups receiving either 33,000IU recombinant human erythropoietin intravenously daily for 3 days or placebo as an add-on therapy to methylprednisolone. The primary outcome parameter was change in retinal nerve fiber layer (RNFL) thickness after 16 weeks. Secondary outcome parameters included optic nerve atrophy as assessed by magnetic resonance imaging, and changes in visual acuity, visual field, and visual evoked potentials (VEPs). RESULTS: Forty patients were assigned to the treatment groups (21/19 erythropoietin/placebo). Safety monitoring revealed no relevant issues. Thirty-seven patients (20/17 erythropoietin/placebo) were analyzed for the primary endpoint according to the intention-to-treat protocol. RNFL thinning was less apparent after erythropoietin treatment. Thickness of the RNFL decreased by a median of 7.5µm by week 16 (mean ± standard deviation, 10.55 ± 17.54µm) compared to a median of 16.0µm (22.65 ± 29.18µm) in the placebo group (p = 0.0357). Decrease in retrobulbar diameter of the optic nerve was smaller in the erythropoietin group (p = 0.0112). VEP latencies at week 16 were shorter in erythropoietin-treated patients than in the placebo group (p = 0.0011). Testing of visual functions revealed trends toward an improved outcome after erythropoietin treatment. INTERPRETATION: These results give the first indications that erythropoietin might be neuroprotective in optic neuritis.

Pattern of gray matter volumes related to retinal thickness and its association with cognitive function in relapsing-remitting MS.

BACKGROUND: Neurodegeneration in multiple sclerosis (MS) may be investigated in the visual system as optical coherence tomography (OCT) and magnetic resonance imaging (MRI) allows examining structural integrity in detail. The association between thickness of retinal layers and focal cortical volumes beyond the primary visual system has not been thoroughly investigated. OBJECTIVE: To investigate the association between focal cortical volume and thickness of retinal layers. METHODS: Fifty-four patients (relapsing-remitting MS, mean age 40.5 years, mean disease duration 7.6 years, median EDSS 2) underwent OCT and MRI. The association between focal cortical volume and OCT measurements was investigated with voxel-based morphometry (VBM). Patterns of association were determined with Yeo's functional network atlas and the Harvard-Oxford cortical atlas. We used GEE models with cortical volumes from the FreeSurfer parcellation to confirm VBM results. Post hoc, we analyzed the association between OCT, focal cortical volumes, and an extended neuropsychological assessment in a subgroup of 14 patients. RESULTS: Macular retinal nerve fiber layer (mRNFL) and ganglion cell /inner plexiform layer (GCIPL) showed a robust association with mainly the insular cortex and the cingulate cortex. VBM findings were confirmed with FreeSurfer volumes. The post hoc analysis detected significant correlations between both OCT outcomes and cognition. CONCLUSION: Besides the primary visual system, OCT outcomes show a correlation pattern with cortical regions that are known to be important for cognitive performance, predominantly the insula in both hemispheres. Thus, OCT should be further investigated as a marker for neurodegeneration in MS.

Detection of retinal changes in idiopathic Parkinson's disease using high-resolution optical coherence tomography and heidelberg retina tomography.

PURPOSE: The study was performed to analyse the retina of patients with Parkinson's disease (PD) for morphological changes compared to healthy controls (HC) using spectral-domain optical coherence tomography (SD-OCT) and confocal scanning laser ophthalmoscopy. METHODS: We enrolled 108 patients with idiopathic PD and 165 HC. All study participants underwent an ophthalmological examination to exclude ophthalmological disorder potentially interfering with the retinal analyses. Peripapillary retinal nerve fibre layer (RNFL) thickness and macular thickness and volume were measured by a SD-OCT device (Heidelberg Spectralis(®) ). Stereometric parameters of the optic disc were acquired by Heidelberg Retina Tomograph (HRT III). RESULTS: The RNFL thickness did not significantly differ between patients with PD and HC. The thickness of the central minimum and the centre of the macular area were significantly reduced in patients with PD, while the total macular volume did not significantly differ between the groups. Furthermore, we noted an inverse correlation between the central minimum thickness and the disease severity (assessed by the Hoehn and Yahr scale). HRT data showed no significant differences. CONCLUSION: The HRT device and the RNFL measurements of the SD-OCT did not prove to be a clinically valid diagnostic tool to distinguish eyes of patients with PD and HC. However, the macular region and especially the foveola (central minimum) with the highest density of photoreceptor cells seem to be more sensitive and might be potential biomarkers.

Scanning laser polarimetry and spectral domain optical coherence tomography for the detection of retinal changes in Parkinson's disease.

PURPOSE: Whether retinal degeneration is part of the degenerative processes in patients with Parkinson's disease (PD) is still unclear. This cross-sectional study was undertaken to compare the retinal morphology of patients with PD and healthy controls using spectral domain optical coherence tomography (SD-OCT) and scanning laser polarimetry (SLP). METHODS: Both eyes of patients with PD (n = 108) and healthy controls (n = 165) were examined using SD-OCT and SLP on the same day. Data on the thickness of the retinal nerve fibre layer (RNFL) of all quadrants and the macular area were acquired by OCT (Cirrus, Zeiss). The SLP device (Glaucoma diagnostics (GDx), Zeiss) measured the RNFL and calculated the nerve fibre index (NFI). All patients and probands were checked for concomitant ocular disorders by an ophthalmologist. Visual acuity, intraocular pressure (IOP), objective refraction and the anterior and posterior segment were assessed. RESULTS: Patients with PD showed a reduced macular volume and a reduced central subfield thickness in OCT examinations. The RNFL in the different quadrants did not differ significantly from that of controls. SLP data showed a reduced average RNFL thickness, a decreased thickness of the inferior quadrant and an increase of the NFI in patients with PD. CONCLUSION: PD may be associated with reduced thickness and volume of the macula and a reduced thickness of the RNFL in the inferior quadrant of the retina. Investigations using SD-OCT and SLP revealed distinct but significant differences between patients with PD and healthy controls.