Visual signs and symptoms in patients with the visual variant of Alzheimer disease.

BACKGROUND: Prominent visual symptoms can present in the visual variant of Alzheimer's disease (VVAD). Ophthalmologists have a significant role to play in the early diagnosis of VVAD. METHODS: We retrospectively reviewed the files of ten consecutive patients diagnosed with VVAD. All patients had a full neuro-ophthalmologic examination, a formal neurological and neuro-psychological testing, and cerebral MRI to confirm diagnosis. In addition, functional neuroimaging was obtained in seven patients. RESULTS: The common primary symptom at presentation with all patients was difficulty with near vision (reading difficulty n = 8, "visual blur" in near vision n = 2), and difficulty writing (n = 3). Following assessment, impaired reading and writing skills were evident in 9/10 and 8/10 patients respectively. Median distance visual acuity was 20/25 and at near the median visual acuity was J6. Partial homonymous visual field defect was detected in 80 % (8/10) of the patients. Color vision was impaired in all patients when tested with Ishihara pseudoisochromatic plates, but simple color naming was normal in 8/9 tested patients. Simultanagnosia was present in 8/10 patients. Vision dysfunction corresponded with cerebral MRI findings where parieto-occipital cortical atrophy was observed in all patients. PET scan (5 patients) or SPECT (2 patients) revealed parieto-occipital dysfunction (hypometabolism or hypoperfusion) in all 7 tested patients CONCLUSIONS: Visual difficulties are prominent in VVAD. Dyslexia, incomplete homonymous hemianopia, preserved color identification with abnormal color vision on Ishihara, and simultanagnosia were all symptoms observed frequently in this patient series. Ophthalmologists should be aware of the possibility of neurodegenerative disorders such as VVAD in patients with unexplained visual complaints, in particular reading difficulties.

Detection of Clinically Significant Prostate Cancer Using Magnetic Resonance Imaging-Ultrasound Fusion Targeted Biopsy: A Systematic Review.

CONTEXT: The current standard for diagnosing prostate cancer in men at risk relies on a transrectal ultrasound-guided biopsy test that is blind to the location of the cancer. To increase the accuracy of this diagnostic pathway, a software-based magnetic resonance imaging-ultrasound (MRI-US) fusion targeted biopsy approach has been proposed. OBJECTIVE: Our main objective was to compare the detection rate of clinically significant prostate cancer with software-based MRI-US fusion targeted biopsy against standard biopsy. The two strategies were also compared in terms of detection of all cancers, sampling utility and efficiency, and rate of serious adverse events. The outcomes of different targeted approaches were also compared. EVIDENCE ACQUISITION: We performed a systematic review of PubMed/Medline, Embase (via Ovid), and Cochrane Review databases in December 2013 following the Preferred Reported Items for Systematic reviews and Meta-analysis statement. The risk of bias was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. EVIDENCE SYNTHESIS: Fourteen papers reporting the outcomes of 15 studies (n=2293; range: 13-582) were included. We found that MRI-US fusion targeted biopsies detect more clinically significant cancers (median: 33.3% vs 23.6%; range: 13.2-50% vs 4.8-52%) using fewer cores (median: 9.2 vs 37.1) compared with standard biopsy techniques, respectively. Some studies showed a lower detection rate of all cancer (median: 50.5% vs 43.4%; range: 23.7-82.1% vs 14.3-59%). MRI-US fusion targeted biopsy was able to detect some clinically significant cancers that would have been missed by using only standard biopsy (median: 9.1%; range: 5-16.2%). It was not possible to determine which of the two biopsy approaches led most to serious adverse events because standard and targeted biopsies were performed in the same session. Software-based MRI-US fusion targeted biopsy detected more clinically significant disease than visual targeted biopsy in the only study reporting on this outcome (20.3% vs 15.1%). CONCLUSIONS: Software-based MRI-US fusion targeted biopsy seems to detect more clinically significant cancers deploying fewer cores than standard biopsy. Because there was significant study heterogeneity in patient inclusion, definition of significant cancer, and the protocol used to conduct the standard biopsy, these findings need to be confirmed by further large multicentre validating studies. PATIENT SUMMARY: We compared the ability of standard biopsy to diagnose prostate cancer against a novel approach using software to overlay the images from magnetic resonance imaging and ultrasound to guide biopsies towards the suspicious areas of the prostate. We found consistent findings showing the superiority of this novel targeted approach, although further high-quality evidence is needed to change current practice.

Quest for Orthologs Entails Quest for Tree of Life: In Search of the Gene Stream.

Quest for Orthologs (QfO) is a community effort with the goal to improve and benchmark orthology predictions. As quality assessment assumes prior knowledge on species phylogenies, we investigated the congruency between existing species trees by comparing the relationships of 147 QfO reference organisms from six Tree of Life (ToL)/species tree projects: The National Center for Biotechnology Information (NCBI) taxonomy, Opentree of Life, the sequenced species/species ToL, the 16S ribosomal RNA (rRNA) database, and trees published by Ciccarelli et al. (Ciccarelli FD, et al. 2006. Toward automatic reconstruction of a highly resolved tree of life. Science 311:1283-1287) and by Huerta-Cepas et al. (Huerta-Cepas J, Marcet-Houben M, Gabaldon T. 2014. A nested phylogenetic reconstruction approach provides scalable resolution in the eukaryotic Tree Of Life. PeerJ PrePrints 2:223) Our study reveals that each species tree suggests a different phylogeny: 87 of the 146 (60%) possible splits of a dichotomous and rooted tree are congruent, while all other splits are incongruent in at least one of the species trees. Topological differences are observed not only at deep speciation events, but also within younger clades, such as Hominidae, Rodentia, Laurasiatheria, or rosids. The evolutionary relationships of 27 archaea and bacteria are highly inconsistent. By assessing 458,108 gene trees from 65 genomes, we show that consistent species topologies are more often supported by gene phylogenies than contradicting ones. The largest concordant species tree includes 77 of the QfO reference organisms at the most. Results are summarized in the form of a consensus ToL (http://swisstree.vital-it.ch/species_tree) that can serve different benchmarking purposes.

Does chronic nicotine consumption influence visual backward masking in schizophrenia and schizotypy ?

Nicotine consumption is higher for people within the schizophrenia spectrum compared to controls. This observation supports the self-medication hypothesis, that nicotine relieves symptoms in, for example, schizophrenia patients. We tested whether performance in an endophenotype of schizophrenia (visual backward masking, VBM) is modulated by nicotine consumption in i) smoking and non-smoking schizophrenia patients, their first-degree relatives, and age-matched controls, ii) non-smoking and smoking university students, and iii) non-smoking, early and late onset nicotine smokers. Overall, our results confirmed that VBM deficits are an endophenotype of schizophrenia, i.e., deficits were highest in patients, followed by their relatives, students scoring high in Cognitive Disorganisation, and controls. Moreover, we found i) beneficial effects of chronic nicotine consumption on VBM performance, in particular with increasing age, and ii) little impact of clinical status. alone or in interactionwith nicotine consumption on VBMperformance. Given the younger age of undergraduate students (up to 30 years) versus controls and patients (up to 66 years),we propose that age-dependent VBMdeficits emergewhen schizotypy effects are targeted in populations of a larger age range, but that nicotine consumption might counteract these deficits (supporting the self-medication hypothesis).

Refractory subretinal fluid in patients with neovascular age-related macular degeneration treated with intravitreal ranibizumab: visual acuity outcome.

PURPOSE: To investigate the functional outcome of eyes with neovascular AMD (nAMD) and subretinal fluid (SRF) refractory to treatment with ranibizumab. METHODS: Retrospective chart review of consecutive treatment-refractory SRF in nAMD despite monthly ranibizumab injections during 12 months or more. Data were evaluated for baseline characteristics, location of the refractory SRF, mean visual acuity (VA) change, number of injections, and timepoint of first complete disappearance of SRF. RESULTS: Forty-five eyes in 44 patients (mean age of 76 years) were included. The mean follow-up was 32.4 months (range 12-73 months). The mean number of injections was 11.6 in the first year and 27.5 over follow-up. The refractory SRF was located subfoveally in 66.7 %. In 12 eyes (26.7 %), complete absorption of SRF was found after a mean of 22.6 months (range, 13-41 months). Mean VA increased by 10.4, 8.2, and 8.6 letters by month 12, 24, and 36, respectively. CONCLUSIONS: Neovascular AMD with SRF refractory to monthly retreatment with ranibizumab may still allow good and maintained visual improvement, even if the fluid is located subfoveally. SRF may progressively absorb under continuous monthly treatment. The necessity to treat refractory SRF with monthly injections could be questioned and would need future investigations.

Discrepancy between Visual Acuity and Microperimetry in AMD Patients: Visual Acuity Appears as an Inadequate Parameter to Test Macular Function.

BACKGROUND: Best corrected visual acuity (BCVA) of 0.8 or above in AMD patients can sometimes correspond to poor macular function inducing a serious visual handicap. Microperimetry can be used to objectivize this difference. PATIENTS AND METHODS: A retrospective study was undertaken on 233 files of AMD patients of whom 82 had had a microperimetry. BCVA was compared with microperimetry performance. All examinations were performed in an identical setting by the same team of 3 persons. RESULTS: Among the 82 patients included, 32 (39.0%) had a BCVA equal to or above 0.8 even though their microperimetry performance was lower than 200/560 db. 10 of them (12.2% of total) had an even poorer microperimetry below 120/560 db indicating poor macular function. CONCLUSIONS: More than a third of the AMD patients had a bad or very bad microperimetry performance in parallel with a good visual acuity. Microperimetry is a valuable tool to assess and follow real macular function in AMD patients when visual acuity alone can be misleading.

Impact of examinees' stereopsis and near visual acuity on laparoscopic virtual reality performance.

PURPOSE: Laparoscopic surgery represents specific challenges, such as the reduction of a three-dimensional anatomic environment to two dimensions. The aim of this study was to investigate the impact of the loss of the third dimension on laparoscopic virtual reality (VR) performance. METHODS: We compared a group of examinees with impaired stereopsis (group 1, n = 28) to a group with accurate stereopsis (group 2, n = 29). The primary outcome was the difference between the mean total score (MTS) of all tasks taken together and the performance in task 3 (eye-hand coordination), which was a priori considered to be the most dependent on intact stereopsis. RESULTS: The MTS and performance in task 3 tended to be slightly, but not significantly, better in group 2 than in group 1 [MTS: -0.12 (95 % CI -0.32, 0.08; p = 0.234); task 3: -0.09 (95 % CI -0.29, 0.11; p = 0.385)]. The difference of MTS between simulated impaired stereopsis between group 2 (by attaching an eye patch on the adominant eye in the 2nd run) and the first run of group 1 was not significant (MTS: p = 0.981; task 3: p = 0.527). CONCLUSION: We were unable to demonstrate an impact of impaired examinees' stereopsis on laparoscopic VR performance. Individuals with accurate stereopsis seem to be able to compensate for the loss of the third dimension in laparoscopic VR simulations.

Identification of two novel mutations in CDHR1 in consanguineous Spanish families with autosomal recessive retinal dystrophy.

Inherited retinal dystrophies present extensive phenotypic and genetic heterogeneity, posing a challenge for patients' molecular and clinical diagnoses. In this study, we wanted to clinically characterize and investigate the molecular etiology of an atypical form of autosomal recessive retinal dystrophy in two consanguineous Spanish families. Affected members of the respective families exhibited an array of clinical features including reduced visual acuity, photophobia, defective color vision, reduced or absent ERG responses, macular atrophy and pigmentary deposits in the peripheral retina. Genetic investigation included autozygosity mapping coupled with exome sequencing in the first family, whereas autozygome-guided candidate gene screening was performed by means of Sanger DNA sequencing in the second family. Our approach revealed nucleotide changes in CDHR1; a homozygous missense variant (c.1720C > G, p.P574A) and a homozygous single base transition (c.1485 + 2T > C) affecting the canonical 5' splice site of intron 13, respectively. Both changes co-segregated with the disease and were absent among cohorts of unrelated control individuals. To date, only five mutations in CDHR1 have been identified, all resulting in premature stop codons leading to mRNA nonsense mediated decay. Our work reports two previously unidentified homozygous mutations in CDHR1 further expanding the mutational spectrum of this gene.