Multiscale methods for shape constraints in deconvolution: Confidence statements for qualitative features

We derive multiscale statistics for deconvolution in order to detect qualitative features of the unknown density. An important example covered within this framework is to test for local monotonicity on all scales simultaneously. We investigate the moderately ill-posed setting, where the Fourier transform of the error density in the deconvolution model is of polynomial decay. For multiscale testing, we consider a calibration, motivated by the modulus of continuity of Brownian motion. We investigate the performance of our results from both the theoretical and simulation based point of view. A major consequence of our work is that the detection of qualitative features of a density in a deconvolution problem is a doable task, although the minimax rates for pointwise estimation are very slow.

Empfehlungen zur Diagnostik und Therapie der behavioralen und psychologischen Symptome der Demenz (BPSD)

In patients with dementia, Behavioral and Psychological Symptoms of Dementia (BPSD) are frequent findings that accompany deficits caused by cognitive impairment and thus complicate diagnostics, therapy and care. BPSD are a burden both for affected individuals as well as care-givers, and represent a significant challenge for therapy of a patient population with high degree of multi-morbidity. The goal of this therapy-guideline issued by swiss professional associations is to present guidance regarding therapy of BPSD as attendant symptoms in dementia, based on evidence as well as clinical experience. Here it appears to be of particular importance to take into account professional experience, as at this point for most therapeutic options no sufficiently controlled clinical trials are available. A critical discussion of pharmaco-therapeutic intervention is necessary, as this patient-population is particularly vulnerable for medication side-effects. Finally, a particular emphasis is placed on incorporating and systematically reporting psycho-social and nursing options therapeutic intervention.

The role of anti-VEGF agents in myopic choroidal neovascularization: Current standards and future outlook

Introduction The global prevalence of pathologic myopia is 0.9-3.1%, and visual impairment is found in 0.1-0.5% of European and 0.2-1.4% of Asian studies. Myopic choroidal neovascularization (mCNV) affects 5.2-11.3% of pathologic myopia patients and is a leading cause of vision impairment in the working-age population. Characteristic morphological changes and visual-acuity decrease are diagnostic features. Vascular-Endothelial-Growth-Factor (VEGF) has been identified as a trigger for pathologic neovascularization in these highly myopic patients. Areas Covered We cover the epidemiology, pathology and diagnostic aspects of mCNV. The history of therapeutic interventions is described, followed by an overview of current standard-of-care (SOC)-blocking VEGF using bevacizumab (off-label), ranibizumab or aflibercept and improving vision up to 13.5-14.4 letters. Despite good efficacy, an unmet medical need remains. We summarize ongoing and future developments of new drugs to treat or potentially cure mCNV. Expert Opinion mCNV is a major global health concern. Early detection and treatment is key for a satisfying outcome. The current SOC, VEGF inhibitors, affords good therapeutic efficacy and reasonable disease stabilization with few intravitreal treatments per year. However, the long-term prognosis is still unsatisfactory, and side-effects like chorioretinal atrophy development are of concern. Therefore, efforts should be intensified to develop more effective therapies.

Oral Lutein Supplementation Enhances Macular Pigment Density and Contrast Sensitivity but Not in Combination With Polyunsaturated Fatty Acids.

Purpose It has been shown that lutein and zeaxanthin accumulate in the macula where they enhance contrast sensitivity and may reduce the risk of progression to advanced age-related macular degeneration (AMD). Furthermore, omega-3 long-chain polyunsaturated fatty acids (PUFA) might further reduce this risk. However, controversy exists regarding whether PUFA may reduce the bioavailability of lutein. Methods This was a prospective 12-month, randomized, open label study evaluating the effect of supplementation with lutein, other antioxidants, and minerals on contrast sensitivity (CS) and macular pigment optical density (MPOD) in patients with age-related maculopathy. A total of 79 patients were randomized to either lutein (10 mg) and antioxidant supplement or lutein and antioxidant supplement in combination with PUFA. Patients received supplementation for a period of 6 months and were followed for a total of 12 months. Results Serum lutein and zeaxanthin increased significantly by the first follow-up visit at 1 month, and remained elevated throughout the intervention period of 6 months in the lutein-only group but not in the lutein+PUFA group. Macular pigment optical density and CS increased significantly in the lutein-only group (P < 0.005) but not in the lutein+PUFA group (P = 0.059) compared to baseline. Best-corrected visual acuity remained unchanged during the entire study period in both groups. Conclusions Addition of PUFA may reduce the bioavailability of lutein and therefore lessen the beneficial effect on macular pigment and CS. This needs to be considered when prescribing lutein supplements to patients with low lutein levels. (ClinicalTrials.gov number, NCT00563979.).

HLA-A29-POSITIVE BIRDSHOT CHORIORETINOPATHY IN AN AFRICAN AMERICAN PATIENT.

PURPOSE: To report the first documented case of HLA-A29-positive birdshot chorioretinopathy in an African American patient. METHODS: A 51-year-old African American woman presented with a 10-year history of photopsia, progressive decrease in visual acuity, metamorphopsia, and new nyctalopia. Both fundi showed evidence of periphlebitis, arterial attenuation, macular edema, and diffuse chorioretinal atrophy. RESULTS: Fluorescein angiography revealed diffuse vascular leakage, and indocyanine green showed evenly distributed and symmetrical hypofluorescent spots, which were difficult to appreciate on fundoscopy. Workup revealed a positive HLA-A29 and was negative for sarcoid, tuberculosis, and syphilis. CONCLUSION: Birdshot chorioretinopathy overwhelmingly affects non-Hispanic Caucasians, but there have been rare reported cases in other ethnicities including Hispanics and African Americans. This patient's ethnicity may have contributed to the 10-year delay in diagnosis. To our knowledge, this is the first documented HLA-A29 positive case of birdshot chorioretinopathy in an African American. HLA-A29 may be a useful supportive test in cases with classic clinical presentation in non-Caucasian patients to enable the correct diagnose in a timely manner.

Differentiation of Diabetic Macular Edema From Pseudophakic Cystoid Macular Edema by Spectral-Domain Optical Coherence Tomography.

PURPOSE: To differentiate diabetic macular edema (DME) from pseudophakic cystoid macular edema (PCME) based solely on spectral-domain optical coherence tomography (SD-OCT). METHODS: This cross-sectional study included 134 participants: 49 with PCME, 60 with DME, and 25 with diabetic retinopathy (DR) and ME after cataract surgery. First, two unmasked experts classified the 25 DR patients after cataract surgery as either DME, PCME, or mixed-pattern based on SD-OCT and color-fundus photography. Then all 134 patients were divided into two datasets and graded by two masked readers according to a standardized reading-protocol. Accuracy of the masked readers to differentiate the diseases based on SD-OCT parameters was tested. Parallel to the masked readers, a computer-based algorithm was established using support vector machine (SVM) classifiers to automatically differentiate disease entities. RESULTS: The masked readers assigned 92.5% SD-OCT images to the correct clinical diagnose. The classifier-accuracy trained and tested on dataset 1 was 95.8%. The classifier-accuracy trained on dataset 1 and tested on dataset 2 to differentiate PCME from DME was 90.2%. The classifier-accuracy trained and tested on dataset 2 to differentiate all three diseases was 85.5%. In particular, higher central-retinal thickness/retinal-volume ratio, absence of an epiretinal-membrane, and solely inner nuclear layer (INL)-cysts indicated PCME, whereas higher outer nuclear layer (ONL)/INL ratio, the absence of subretinal fluid, presence of hard exudates, microaneurysms, and ganglion cell layer and/or retinal nerve fiber layer cysts strongly favored DME in this model. CONCLUSIONS: Based on the evaluation of SD-OCT, PCME can be differentiated from DME by masked reader evaluation, and by automated analysis, even in DR patients with ME after cataract surgery. The automated classifier may help to independently differentiate these two disease entities and is made publicly available.

New associations of classic acute macular neuroretinopathy

PURPOSE: To describe novel underlying associations of classic acute macular neuroretinopathy (AMN). METHODS: Multimodal imaging case series evaluating patients with classic AMN lesions and previously unreported underlying aetiologies. RESULTS: Six patients were included (five women, one man, mean age 30±7 years). Mean distance best corrected visual acuity at initial presentation was 0.21±0.3 logMAR (mean Snellen acuity: 20/30, range 20/15-20/100) and at last follow-up visit 0.09±0.17 logMAR (Snellen acuity: 20/20, range 20/15-20/60). All cases but one had bilateral lesions and showed typical parafoveal hyporeflective lesions on infrared imaging, which corresponded to the hyper-reflectivity in the Henle's layer with attenuation of the external limiting membrane, the ellipsoid zone and interdigitation zone. Underlying diseases included thrombocytopenia and anaemia associated with dengue fever, acute lymphoblastic leukaemia, chronic kidney disease and ulcerative colitis, while Valsalva-like manoeuvre was found to be a potential trigger. Other novel associations included the use of lisdexamphetamine. CONCLUSIONS: Classic AMN may be associated with leukaemia, dengue fever, ulcerative colitis and chronic kidney disease, probably as a result of chorioretinal hypoxia in the setting of thrombocytopenia and anaemia. Adrenergic agonists such as lisdexamphetamine may also contribute to the manifestation of AMN.

Expanded Clinical Spectrum of Multiple Evanescent White Dot Syndrome with Multimodal Imaging

PURPOSE: To evaluate and characterize multiple evanescent white dot syndrome abnormalities with modern multimodal imaging modalities. METHODS: This retrospective cohort study evaluated fundus photography, fluorescein angiography, indocyanine green angiography, optical coherence tomography, enhanced depth imaging optical coherence tomography, short-wavelength autofluorescence, and near-infrared autofluorescence. RESULTS: Thirty-four multiple evanescent white dot syndrome patients with mean age of 28.7 years were studied (range, 14-49 years). Twenty-six patients were women, and eight were men. Initial mean visual acuity was 0.41 logMAR. Final mean visual acuity was 0.03 logMAR. Fluorescein angiography shows a variable number of mid retinal early fluorescent dots distributed in a wreathlike pattern, which correlate to fundus photography, fundus autofluorescence, and indocyanine green angiography. Indocyanine green angiography imaging shows the dots and also hypofluorescent, deeper, and larger spots, which are occasionally confluent, demonstrating a large plaque of deep retinal hypofluorescence. Optical coherence tomography imaging shows multifocal debris centered at and around the ellipsoid layer, corresponding to the location of spots seen with photography, indocyanine green angiography, and fluorescein angiography. Protrusions of the hyperreflectant material from the ellipsoid layer toward the outer nuclear layer correspond to the location of dots seen with photography, indocyanine green angiography, and fluorescein angiography. CONCLUSION: Multimodal imaging analysis of the retina in patients with multiple evanescent white dot syndrome shows additional features that may help in the diagnosis of the disease and in further understanding its etiology. Multiple evanescent white dot syndrome is predominantly a disease of the outer retina, centered at the ellipsoid zone, but also involving the interdigitation zone and the outer nuclear layer.

RETICULAR PSEUDODRUSEN ON INFRARED IMAGING ARE TOPOGRAPHICALLY DISTINCT FROM SUBRETINAL DRUSENOID DEPOSITS ON EN FACE OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: To evaluate the quantitative and topographic relationship between reticular pseudodrusen (RPD) on infrared reflectance (IR) and subretinal drusenoid deposits (SDD) on en face volumetric spectral domain optical coherence tomography. METHODS: Reticular pseudodrusen were marked on IR images by a masked observer. Subretinal drusenoid deposits were visualized on en face sections of spectral domain optical coherence tomography below the external limiting membrane and identified by a semiautomated technique. Control RPD lesions were generated in a random distribution for each IR image. Binary maps of control and experimental RPD and SDD were merged and analyzed in terms of topographic localization and quantitative drusen load comparison. RESULTS: A total of 54 eyes of 41 patients diagnosed with RPD were included in this study. The average number of RPD lesions on IR images was 320 ± 44.62 compared with 127 ± 26.02 SDD lesions on en face (P < 0.001). The majority of RPD lesions did not overlap with SDD lesions and were located >30 μm away (92%). The percentage of total SDD lesions overlapping RPD was 2.91 ± 0.87% compared with 1.73 ± 0.68% overlapping control RPD lesions (P < 0.05). The percentage of total SDD lesions between 1 and 3 pixels of the nearest RPD lesion was 5.08 ± 1.40% compared with 3.33 ± 1.07% between 1 and 3 pixels of the nearest control RPD lesion (P < 0.05). CONCLUSION: This study identified significantly more RPD lesions on IR compared with SDD lesions on en face spectral domain optical coherence tomography and found that a large majority of SDD (>90% of lesions) were >30 μm away from the nearest RPD. Together, our findings indicate that RPD and SDD are two entities that are only occasionally topographically associated, suggesting that at some stage in their development, they may be pathologically related.