Etienne M. Schönbach

Early subclinical macular edema in eyes with uveal melanoma: association with future cystoid macular edema.

PURPOSE To determine the frequency of early subclinical macular edema in eyes with uveal melanoma and its association with future cystoid macular edema (CME). DESIGN Retrospective cohort study. PARTICIPANTS A total of 306 patients with uveal melanoma; 260 patients had follow-up of 1 or more years after plaque radiotherapy (follow-up cohort). METHODS Review of medical records and spectral-domain optical coherence tomography (OCT) images. MAIN OUTCOME MEASURES Frequency of early subclinical macular edema (increased central macular thickness of >10 μm without cystoid changes before or at 4 months after plaque radiotherapy); rate of future CME. RESULTS At baseline, 164 patients (54%) had subclinical macular edema in the involved eye. On multivariate analysis, factors associated with subclinical macular edema at baseline were increasing tumor diameter (P = 0.001), increasing tumor thickness (P = 0.010), and subretinal fluid (P = 0.001). Of 260 patients in the follow-up cohort, 105 (40%) developed CME during a median follow-up of 31 months (mean, 34; range, 12-70 months). Eyes with subclinical macular edema at baseline (and at 4 months after plaque radiotherapy) had a significantly higher rate of future CME (n = 66; 50%) compared with eyes without subclinical macular edema at baseline (n = 39; 30%) (P = 0.005; hazard ratio, 1.77; 95% confidence interval, 1.19-2.64). On multivariate analysis, the factors associated with future development of CME included female gender (P = 0.004), increasing tumor thickness (P < 0.001), decreasing tumor distance to foveola (P = 0.002), hemorrhage over tumor (P = 0.017), and increased CMT of >10% at baseline in the involved eyes compared with the opposite eyes (P = 0.012). CONCLUSIONS Subclinical macular edema is common in eyes with uveal melanoma before and at 4 months after plaque radiotherapy and is associated with initial larger tumor size. Eyes with early subclinical macular edema are at significantly higher risk for future CME. These findings suggest that tumor-related factors, most likely mediated through proinflammatory cytokines, may play an important role in development of post-radiation CME.

Headache in acute ischaemic stroke: a lesion mapping study

Headache is a common symptom in acute ischaemic stroke, but the underlying mechanisms are incompletely understood. The aim of this lesion mapping study was to identify brain regions, which are related to the development of headache in acute ischaemic stroke. Patients with acute ischaemic stroke (n = 100) were assessed by brain MRI at 3 T including diffusion weighted imaging. We included 50 patients with stroke and headache as well as 50 patients with stroke but no headache symptoms. Infarcts were manually outlined and images were transformed into standard stereotaxic space using non-linear warping. Voxel-wise overlap and subtraction analyses of lesions as well as non-parametric statistics were conducted. The same analyses were carried out by flipping of left-sided lesions, so that all strokes were transformed to the same hemisphere. Between the headache group as well as the non-headache there was no difference in infarct volumes, in the distribution of affected vascular beds or in the clinical severity of strokes. The headache phenotype was tension-type like in most cases. Subtraction analysis revealed that in headache sufferers infarctions were more often distributed in two well-known areas of the central pain matrix: the insula and the somatosensory cortex. This result was confirmed in the flipped analysis and by non-parametric statistical testing (whole brain corrected P-value < 0.01). To the best of our knowledge, this is the first lesion mapping study investigating potential lesional patterns associated with headache in acute ischaemic stroke. Insular strokes turned out to be strongly associated with headache. As the insular cortex is a well-established region in pain processing, our results suggest that, at least in a subgroup of patients, acute stroke-related headache might be centrally driven.

Smoking Cessation Related to Improved Patient-Reported Pain Scores Following Spinal Care in Geriatric Patients

Introduction: We examined rates of smoking cessation and the effect of smoking cessation on pain and disability scores in a geriatric patient population. Methods: Prospectively maintained database records of 6779 patients treated for painful spinal disorders were examined. The mean duration of care was 8 months. Multivariate statistical analysis was performed with independent variables including smoking status, secondary gain status, gender, treatment type, depression, and age. Results: Of the patients seeking care for painful spinal disorders, 8.9% over the age of 55 smoked compared with 23.9% of those under 55 years of age. Rates of smoking cessation did not differ for those older than 55 years (25.1%) and younger patients (26.1%). Current smokers in both age-groups reported greater pain than those who had never smoked in all pain ratings (P < .001). Mean improvement in reported pain over the course of treatment was significantly different in nonsmokers and current smokers in both age-groups (P < .001). Those who quit smoking during the course of care reported greater improvement in pain than those who continued to smoke. The mean improvement in pain ratings was clinically significant in patients in all 3 groups of nonsmokers whereas those who continued to smoke had no clinically significant improvement in reported pain. Conclusion: The results support the need for smoking cessation programs, given a strong association between improved patient-reported pain and smoking cessation. Fewer older patients smoke but they are equally likely to quit.

FUNDUS AUTOFLUORESCENCE IN A SUBCLINICAL CASE OF BEST DISEASE.

Purpose: To demonstrate the usefulness of fundus autofluorescence for diagnosing a subclinical case of Best disease. Results: We describe a 27-year-old white woman without central visual symptoms, visual acuity of 20/12 in both eyes, carrying the previously reported p.Tyr227Cys mutation in the BEST1 gene. Although electrooculography, microperimetry (MP-1), and spectral-domain optical coherence tomography did not reveal unequivocal pathology, fundus autofluorescence imaging allowed to clearly detect a phenotypic correlate of Best disease, namely small areas of significantly increased fundus autofluorescence signals. Conclusion: This report suggests that in selected subclinical cases, fundus autofluorescence may be more sensitive than the MP-1 and spectral-domain optical coherence tomography in the detection of subclinical cases of BEST1-associated retinopathy.

Association of clinical headache features with stroke location: An MRI voxel-based symptom lesion mapping study.

Background We have recently shown that the presence of headache in ischemic stroke is associated with lesions of the insular cortex. The aim of this post-hoc subgroup analysis was to investigate the association of specific headache features with stroke location in patients with acute ischemic stroke. Methods In this observational study, patients (mean age: 61.5, 58% males) with ischemic stroke and acute headache (n = 49) were investigated. Infarcts were manually outlined on 3D diffusion weighted magnetic resonance imaging (MRI) scans and transformed into standard stereotaxic space; lesions of the left hemisphere were mirrored in the x-axis to allow a voxel-wise group analysis of all patients. We analyzed the association of lesion location and the following phenotypical characteristics by voxel-based symptom lesion mapping: Headache intensity, different qualities of headache (pulsating, tension-type like and stabbing), and the presence of nausea, of cranial autonomic symptoms and of light or noise sensitivity. Results Headache intensity was associated with lesions of the posterior insula, the operculum and the cerebellum. “Pulsating” headache occurred with widespread cortical and subcortical strokes. The presence of “tension-like” and “stabbing” headache was not related to specific lesion patterns. Nausea was associated with lesions in the posterior circulation territory. Cranial-autonomic symptoms were related to lesions of the parietal lobe, the somatosensory cortex (SI) and the middle temporal cortex. The presence of noise sensitivity was associated with cerebellar lesions, whereas light sensitivity was not related to specific lesions in our sample. Conclusion Headache phenotype in ischemic stroke appears to be related to specific ischemic lesion patterns.

7-Hexagon Multifocal Electroretinography for an Objective Functional Assessment of the Macula in 14 Seconds

Purpose: We present the multifocal electroretinogram (mfERG) with a 7-hexagon array as an objective test of macular function that can be recorded in 14 s. We provide normal values and investigate its reproducibility and validity. Methods: Healthy participants underwent mfERG testing according to International Society for Clinical Electrophysiology of Vision (ISCEV) standards using the Espion Profile/D310 multifocal ERG system (Diagnosys, LLC, Lowell, MA, USA). One standard recording of a 61-hexagon array and 2 repeated recordings of a custom 7-hexagon array were obtained. Results: A total of 13 subjects (mean age 46.9 years) were included. The median response densities were 12.5 nV/deg2 in the center and 5.2 nV/deg2 in the periphery. Intereye correlations were strong in both the center (ρCenter = 0.821; p < 0.0001) and the periphery (ρPeriphery = 0.862; p < 0.0001). Intraeye correlations were even stronger: ρCenter = 0.904 with p < 0.0001 and ρPeriphery = 0.955 with p < 0.0001. Bland-Altman plots demonstrated an acceptable retest mean difference in both the center and periphery, and narrow limits of agreement. We found strong correlations of the center (ρCenter = 0.826; p < 0.0001) and periphery (ρPeriphery = 0.848; p < 0.0001), with recordings obtained by the 61-hexagon method. Conclusions: The 7-hexagon mfERG provides reproducible results in agreement with results obtained according to the ISCEV standard.

Metrics and Acquisition Modes for Fixation Stability as a Visual Function Biomarker

Purpose To compare different metrics and acquisition modes of fixation stability as a new visual function biomarker in a large cohort of patients with ABCA4-related Stargardt disease from the multicenter prospective ProgStar study. Methods Fixation was tested during a separate fixation exam and also dynamically during a sensitivity exam, using fundus-tracking microperimetry (Nidek MP-1). Fixation data were analyzed using the bivariate contour ellipse area (BCEA), the 2/4 degree method, and the Fujii classification. Results In a total of 235 patients, the mean BCEA was larger when measured during the sensitivity exam (418 eyes; 12.5 vs. 4.6 deg2 during the fixation task in 427 eyes). Correlations between the two tests were generally weak. Fixation stability during the sensitivity test was significantly correlated with visual acuity. Comparing the BCEA values and the corresponding Fujii categories for these eyes revealed ranges of overlap where an eye with one defined BCEA value can fall into each of the three Fujii categories. Conclusions Patients may have limited ability to fixate over defined time periods, which leads to significant differences between shorter and longer measurements of fixation stability. The most appropriate way to use this functional biomarker appears to be using continuous metrics for fixation stability, such as the BCEA, during a macular sensitivity test.

The Progression of the Stargardt Disease Type 4 (ProgStar-4) Study: Design and Baseline Characteristics (ProgStar-4 Report No. 1)

Background/Aims: To describe the design and baseline characteristics of patients enrolled in the multicenter, prospective natural history study of Stargardt disease type 4. Methods: Fifteen eligible patients aged 6 years and older at baseline, harboring disease-causing variants in the PROM1 gene, and with specified ocular lesions were enrolled. They were examined at baseline using a standard protocol, with 6 monthly follow-up visits for a 2-year period including best-corrected ETDRS visual acuity, spectral-domain optical coherence tomography, fundus autofluorescence (FAF), mesopic and scotopic microperimetry (MP). Areas of definitely decreased FAF (DDAF) and questionably decreased FAF were outlined and quantified on FAF images. Results: Amongst the 15 patients (29 eyes) that were enrolled at 5 centers in the USA and Europe, 10 eyes (34.5%) had areas of DDAF with an average lesion area of 3.2 ± 3.5 mm2 (range 0.36–10.39 mm2) at baseline. The mean retinal sensitivity of the posterior pole derived from mesopic MP was 8.8 ± 5.8 dB. Conclusions: Data on disease progression in PROM1-related retinopathy from this study will contribute to the characterization of the natural history of disease and the exploration of the utility of several modalities to track progression and therefore to potentially be used in future interventional clinical trials.