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Apathy is a common behavioral symptom of Huntington disease (HD). This systematic review describes current evidence on the pathophysiology, assessment, and frequency of apathy in HD.This systematic review was conducted in accordance with PRISMA guidelines. Using a comprehensive search strategy, the investigators searched the MEDLINE, Embase, and PsycINFO databases. All studies that evaluated apathy in HD patients with a valid scale and reported apathy frequency or scores were included. Apathy scores were analyzed by mean or standardized mean differences in accordance with Cochrane guidelines.A total of 1,085 records were screened and 80 studies were ultimately included. The Problem Behaviors Assessment-Short was the most frequently used apathy assessment tool. Apathy frequency generally ranged from 10%-33% in premanifest HD to 24%-76% in manifest HD. A meta-analysis of 5,311 records of patients with premanifest HD showed significantly higher apathy scores, with a standardized mean difference of 0.41 (CI=0.29-0.52; p0.001). A comparison of 1,247 patients showed significantly higher apathy scores in manifest than premanifest HD, with a mean difference of 1.87 (CI=1.48-2.26; p0.001). There was evidence of involvement of various cortical and subcortical brain regions in HD patients with apathy.Apathy was more frequent among individuals with premanifest HD compared with those in a control group and among individuals with manifest HD compared with those with premanifest HD. Considering the complexity and unique pattern of development in neurodegenerative disease, further studies are required to explore the pathophysiology of apathy in HD.

Age-related macular degeneration (AMD) is a complex, multifactorial, progressive retinal disease that affects millions of people worldwide and has become the leading cause of visual impairment in developed countries. The disease etiopathogenesis is not understood fully, although many triggers and processes that lead to dysfunction and degeneration of the retinal pigment epithelium (RPE) have already been identified. Thus, the lack of cellular control of oxidative stress, altered proteostasis, dysfunction of lipid homeostasis, and mitochondrial dysfunction form an internal feedback loop that causes the RPE to fail and allows accumulation of abnormal misfolded proteins and abnormal lipids that will form drusen. An inadequate antioxidant response, deficits in autophagy mechanisms, and dysregulation of the extracellular matrix (ECM) help to increase the deposition of abnormal drusen material over time. The drusen then act as inflammatory centers that trigger chronic inflammation of the subretinal space in which microglia and recruited macrophages are also involved, and where the complement system is a key component. Choriocapillaris degeneration and nutritional influences are also classic elements recognized in the AMD pathophysiology. The genetic component of the disease is embodied in the recognition of the described risk or protective polymorphisms of some complement and ECM related genes (mainly CFH and ARMS2/HTRA1). Thus, carriers of the risk haplotype at ARMS2/HTRA1 have a higher risk of developing late AMD at a younger age. Finally, gut microbiota and epigenetics may play a role in modulating the progression to advanced AMD with the presence of local inflammatory conditions. Because of multiple implicated processes, different complex combinations of treatments will probably be the best option to obtain the best visual results; they in turn will differ depending on the type and spectrum of disease affecting individual patients or the disease stage in each patient at a specific moment. This will undoubtedly lead to personalized medicine for control and hopefully find a future cure. This necessitates the continued unraveling of all the processes involved in the pathogenesis of AMD that must be understood to devise the combinations of treatments for different concurrent or subsequent problems.

Background There are few clinical data on retinal involvement after acute exposure to high concentrations mercury and the available reports are based on a small number of patients suffering chronic exposure. The purpose of this paper is to report findings in workers acutely exposed to very high concentrations of mercury vapor with the aim of providing data on a possible direct retinal involvement. Methods Twenty-nine patients and 16 controls were evaluated in a comparative case series. Mercury levels in blood and urine samples, visual acuity (VA), contrast sensitivity (CS), visual field (VF), color discrimination and optical coherence tomography (OCT) were recorded. The pattern reversal visual-evoked potentials (PRVEP), full-field and multifocal electroretinography (ffERG/mfERG), pattern electroretinography (PERG), systemic symptoms, presence of erethism, and electromyography (EMG) were also gathered. A descriptive analysis was performed. The correlations between variables also were studied. In addition, electrophysiological data from those patients with deeper VF defects (group 1) were compared with a normal control group. Results Twenty-six workers exhibited symptoms of erethism. The EMG showed sensorimotor polyneuropathy and multiple mononeuropathy. The VA was slightly affected in 48.27% (n = 14) of subjects. Loss of CS in at least one of four spatial frequencies and color vision alterations occurred in 96.5% (n = 28) and 44.8% (n = 13), respectively. VF alterations were identified in 72.4% (n = 21) patients. No morphologic changes were seen in the OCT scans. Latencies over 100 milliseconds and reduced amplitudes of P100 were found in the PRVEP (p Conclusions In this case series, showed that acute exposure to mercury vapor had a hazardous effect on the visual system. Although neurologic and visual pathway involvement was clearly demonstrated, the differences found compared to control support the existence of a direct functional retinal damage and participation in impaired vision in mercury poisoning.

Background Prevalence of high myopia is continuously increasing, thus, patients affected with staphyloma are abundant worldwide. Assessment of the quality of vision in these patients is mandatory for a proper clinical counselling, specially when undergoing surgical procedures that require intraocular lenses implantation. Thus, the purpose of the study was to assess monochromatic higher order aberrations (HOAs) in highly myopic eyes with staphyloma with or without a dome-shaped macula. Methods Participants underwent spectral-domain optical coherence tomography, ocular axial biometry, dual Scheimpflug photography and integrated Placido disk topography, and Hartmann-Shack wavefront analysis. Five groups were evaluated: a low-moderate myopia control group (n = 31) and four high myopia (≥6.00 diopters) groups: eyes without staphyloma (n = 18), eyes with inferior staphyloma (n = 14), eyes with posterior staphyloma without dome-shaped macula (n = 15) and eyes with posterior staphyloma with dome-shaped macula (n = 17). Subsequently, two new groups (including all participants) were created to assess differences between myopia with and without staphyloma. One-way analysis of covariance was performed using age and lens densitometry as covariates. Results Statistically significant (p ≤ 0.05) differences in anterior corneal fourth-order HOAs were observed between the low-moderate myopia and no-dome-shaped macula (Mean: 0.16 μm) and dome-shaped macula posterior staphyloma groups (Mean: 0.12 μm) in younger patients (≤45 years old). The same groups also showed (p ≤ 0.05) significant differences for anterior corneal primary spherical aberration (Mean: 0.19 and 0.13 μm, respectively). In addition, anterior corneal tetrafoil was significantly higher (p = 0.04) in dome-shaped macula compared to no-dome-shaped macula (Mean: 0.18 vs 0.06 μm, respectively). When all participants were grouped together, significantly lower mean anterior corneal primary spherical aberration (0.15 μm vs. 0.27 μm, p = 0.004) and higher internal primary spherical aberration (0.04 μm vs. -0.06 μm, p = 0.04) was observed in staphyloma compared to no-staphyloma myopic patients. Conclusions Eyes with high myopia and staphyloma have less positive anterior corneal primary spherical aberration and less negative internal primary spherical aberration, suggesting that the anterior corneal surface tends to mimic in a specular fashion the posterior pole profile. This corneal behaviour appears to change in patients older than 45 years.

Rosa M Coco-Martin,1,2 Miguel Diego-Alonso,1,3 W Andres Orduz-Montaña,1 M Rosa Sanabria,1,4 Hortensia Sanchez-Tocino1,3 1Instituto Universitario de Oftalmobiología Aplicada (IOBA), University of Valladolid, Valladolid, Spain; 2Red Temática de Investigación Cooperativa en Salud de Oftalmologia (Oftared), Instituto de Salud Carlos III, Madrid, Spain; 3Department of Ophthalmology, Hospital Universitario Río Hortega, Valladolid, Spain; 4Department of Ophthalmology, Complejo Hospitalario De Palencia, Palencia, SpainCorrespondence: Rosa M Coco-MartinInstituto de Oftalmobiologia Aplicada (IOBA), University of Valladolid, Campus Miguel Delibes, Pº de Belén Nº 17, Valladolid, 47011, SpainTel +34 983423559, ext. 4738Fax +34 983423274Email rosa@ioba.med.uva.esPurpose: To analyze the distribution of inherited retinal diseases (IRDs), describe the clinical characteristics of patients, and determine the percentages of patients with genetic diagnosis in the Castilla y Leon region of Spain.Methods: All patients with an IRD seen in the two major referral units of Castilla y Leon during a 20-year period were included. The ages at symptom onset, diagnosis, and the last visit; sex; family history; history of consanguinity; type of inheritance; status of the fundus and electroretinogram findings; lens and macular status, visual acuity; and visual field data were recorded. Patients were divided into those with retinitis pigmentosa (RP) and all others. Gene mutations were gathered when available.Results: Four hundred eighty-eight patients with IRDs were studied: 216 (44.26%) with RP of which 34 (15.74%) had syndromic diseases, and 272 had other conditions being 161 (59,19%) macular dystrophies. The mean delay in diagnosis was 6– 16.2 years respectively. For the RP group the mean age at the last visit was 47.96± 17,26; mean age of cataract surgery was 48.30 ± 12.01 years; and the foveal area was preserved in 74 (35.07%) patients, atrophic in 101 (47.87%), and edematous in 36 (17.06%). A genetic study had been performed in 58 (26.85%) of patients with RP and 71 (26,1%) of the rest, being indeterminate in 17 (29.31%) out of RP group and 20 (28.16%) out of the others.Conclusion: Clinical characteristics are comparable to other published series. There is a significant delay in diagnosis. The number of patients with IRDs and available genetic diagnosis, thus being possible candidates for undergoing personalized treatments including gene therapy in our region is low and must be improved.Keywords: inherited retinal dystrophies, retinitis pigmentosa, genetic diagnosis, visual acuity, visual field

The striped cucumber beetle, Acalymma vittatum (Fabricius), is an important pest of cucurbit production in the eastern United States, where most commercial producers rely on insecticides to control this pest species. Biological control provides an alternative to insecticide use, but for A. vittatum, top-down control has not been well developed. In the northeastern United States, two parasitoid species, Celatoria setosa (Coquillett) (Diptera: Tachinidae) and Centistes diabroticae (Gahan) (Hymenoptera: Braconidae) have been reported from A. vittatum, but their distribution is poorly known. To determine whether these parasitoid species are attacking A. vittatum in Pennsylvania and the amount of mortality they provide, we characterized the parasitoid dynamics in two distinct efforts. First, we reared parasitoids from beetles captured at two research farms. Second, we focused on one of these farms and dissected beetles to quantify both parasitoid and parasite species attacking A. vittatum. Both efforts confirmed Cl. setosa and Cn. diabroticae, and parasitism rates varied widely between locations and among years (4–60%). Unexpectedly, our dissections revealed that a potentially undescribed nematode species (Howardula sp.) as the most common parasite in the community. We also discovered gregarine protists. Despite being smaller than females, males were more commonly attacked by parasitic species, but we detected no relationship between the size of beetles and abundance of parasitic species in A. vittatum. This work provides a baseline understanding of the parasitoid and parasite community attacking A. vittatum and advances opportunities for conservation biological control using these natural-enemy species.

This study aims to determine the probability of progression of myopic maculopathy according to age. This is a longitudinal observational study of single-center retrospective cohort of Caucasian patients formed by 212 consecutive adults with high myopia. Main outcome measures were age, visual acuity (VA), refractive error (RE), follow-up time, and the macular status assessed at least 5 years apart according to the Meta-Analysis of Pathologic Myopia Study Group. The progression rate was calculated based on per 1000 eyes/year. Multistate models were fitted to identify the predictive factors and to calculate the most probable age of progression onset using the Aalen–Johansen estimator. We studied 220 eyes of 122 Caucasian patients. Mean age was 48.18 ± 14.1, mean follow-up 12.73 ± 5.81 years. One-hundred and fifty-two (69.1%) eyes progressed of category, and 96 (44%) worsened a mean of 0.3 logMAR units during follow-up. The progression rate was 32.21/1000 eyes/year. The probability of progressing increased with age; it was higher in women if there was a family history of myopia, worse VA, higher RE, or wide macular staphyloma. The probability of progressing from category 1 was > 0.6 after 70 years of age; from category 2, it was 0.7 after 70 years; and 0.5 from category 3 after 75 years. If choroidal neovascularization (CNV) appeared, this probability exceeded 0.7 between ages 45 and 55 for all categories. The progression rate is lower than in a Japanese series. The vision worsened with disease progression, and the probability of both happening increased after the age of 70–75. If CNV appears, the risk of progression is very high at the age of 45–55.

High myopia (HM) is defined as an axial length (AL) ≥ 26 mm that may result in various pathologies that constitute pathologic myopia (PM). The PLEX® Elite 9000 (Carl Zeiss AC, Jena, Germany) is a new swept-source optical coherence tomography (SS-OCT) underdevelopment that allows wider, deeper and more detailed posterior-segment visualization; it can acquire ultra-wide OCT angiography (OCTA) or new ultra-wide high-density scans in one image. We assessed the technology’s ability to identify/characterize/quantify staphylomas and posterior pole lesions or image biomarkers in highly myopic Spanish patients and estimate the technology’s potential to detect macular pathology. The instrument acquired 6 × 6 OCTA, 12 × 12 or 6 × 6 OCT cubes, and at least two high-definition spotlight single scans. A hundred consecutive patients (179 eyes; age, 51.4 ± 16.8 years; AL, 28.8 ± 2.33 mm) were recruited in one center for this prospective observational study. Six eyes were excluded because images were not acquired. The most common alterations were perforating scleral vessels (88.8%), classifiable staphyloma (68.7%), vascular folds (43%), extrafoveal retinoschisis (24%), dome-shaped macula (15.6%), and more uncommonly, scleral dehiscence (4.46%), intrachoroidal cavitation (3.35%), and macular pit (2.2%). The retinal thickness of these patients decreased, and the foveal avascular zone increased in the superficial plexus compared with normal eyes. SS-OCT is a novel potent tool that can detect most main posterior pole complications in PM and may provide us with a better understanding of the associated pathologies; some pathologies were identifiable only with this new kind of equipment, such as perforating scleral vessels, which seem to be the most common finding and not so frequently related to choroidal neovascularization, as previously reported.

Because the diet of many herbivorous insects is restricted to closely related taxa with similar chemistry, intercropping with diverse plant communities may reduce both pest populations and reliance on chemical pesticides in agroecosystems. We tested whether the effectiveness of intercropping against herbivorous insects depends on the phylogenetic relatedness of neighboring crops, using butternut squash (Cucurbita moschata) as a focal crop species in a series of different intercropping combinations. We found that increased phylogenetic divergence of neighboring plants could reduce abundance of herbivorous insects, but the effect was only detectable mid-season. In addition, we tested two hypothesized mechanisms for a negative association between phylogenetic distance of neighboring plants and reduced herbivore populations: one, we tested using Y-tube olfactometer and choice cage trials whether diverse volatile cues impede host-plant location by the dominant pest of butternut squash in our experiment, striped cucumber beetle Acalymma vittatum. Two, we recorded predator and parasitoid abundance relative to crop phylodiversity to test whether diverse crops support larger natural-enemy populations that can better control pest species. Our results, however, did not support either hypothesis. Striped cucumber beetles preferentially oriented toward non-host-plant volatiles, and predator populations more often decreased with phylodiversity than increased. Thus, the mechanisms driving associations in the field between phylogenetic divergence and herbivore populations remain unclear.

The aim of this review was to provide an update on the potential of cell therapies to restore or replace damaged and/or lost cells in retinal degenerative and optic nerve diseases, describing the available cell sources and the challenges involved in such treatments when these techniques are applied in real clinical practice. Sources include human fetal retinal stem cells, allogenic cadaveric human cells, adult hippocampal neural stem cells, human CNS stem cells, ciliary pigmented epithelial cells, limbal stem cells, retinal progenitor cells (RPCs), human pluripotent stem cells (PSCs) (including both human embryonic stem cells (ESCs) and human induced pluripotent stem cells (iPSCs)) and mesenchymal stem cells (MSCs). Of these, RPCs, PSCs and MSCs have already entered early-stage clinical trials since they can all differentiate into RPE, photoreceptors or ganglion cells, and have demonstrated safety, while showing some indicators of efficacy. Stem/progenitor cell therapies for retinal diseases still have some drawbacks, such as the inhibition of proliferation and/or differentiation in vitro (with the exception of RPE) and the limited long-term survival and functioning of grafts in vivo. Some other issues remain to be solved concerning the clinical translation of cell-based therapy, including (1) the ability to enrich for specific retinal subtypes; (2) cell survival; (3) cell delivery, which may need to incorporate a scaffold to induce correct cell polarization, which increases the size of the retinotomy in surgery and, therefore, the chance of severe complications; (4) the need to induce a localized retinal detachment to perform the subretinal placement of the transplanted cell; (5) the evaluation of the risk of tumor formation caused by the undifferentiated stem cells and prolific progenitor cells. Despite these challenges, stem/progenitor cells represent the most promising strategy for retinal and optic nerve disease treatment in the near future, and therapeutics assisted by gene techniques, neuroprotective compounds and artificial devices can be applied to fulfil clinical needs.

Background: The aim of this study was to determine the intra-session repeatability and inter-examiner reproducibility of the colour perimetry technique when assessing in vivo macular pigment optical density in age-related macular degeneration patients. Methods: Age-related macular degeneration patients were classified into four groups: early age-related macular degeneration, intermediate age-related macular degeneration, atrophic age-related macular degeneration and neovascular age-related macular degeneration after undergoing fundus photography (TRC 50DX type IA) and spectral-domain optical coherence tomography analysis (Topcon 3D-2000). Central fixation was confirmed in all patients using the MP-1 microperimeter (Nidek, Padua, Italy). To analyse repeatability, one examiner obtained three consecutive macular pigment optical density measures with MonCV3 device (Metrovision, Perenchies, France). To study agreement between two observers, a second examiner performed another macular pigment optical density measurement in random order. Within-subject standard deviation, coefficient of variation, and intraclass correlation coefficient data were obtained. Results: Fifty two (32 females and 20 males) consecutive age-related macular degeneration patients having a mean age of 71.5 ± 8.2 years were recruited. Six had early age-related macular degeneration, 25 had intermediate age-related macular degeneration, 10 had atrophic age-related macular degeneration and 11 had neovascular age-related macular degeneration. For repeatability, coefficient of variation values ranged from 22.3% (neovascular age-related macular degeneration) to 41.0% (atrophic age-related macular degeneration) and intraclass correlation coefficient values from 0.52 (intermediate age-related macular degeneration) to 0.79 (neovascular age-related macular degeneration). For agreement between two examiners, coefficient of variation values ranged from 20.1% (intermediate age-related macular degeneration) to 37.8% (neovascular age-related macular degeneration) and intraclass correlation coefficient values from 0.61 (neovascular age-related macular degeneration) to 0.80 (atrophic age-related macular degeneration). Conclusion: The reliability (intra-session repeatability and inter-examiner reproducibility) of colour perimetry technique to assess macular pigment optical density in age-related macular degeneration patients is only moderate. Thus, it cannot be recommended to be performed when evaluating and monitoring age-related macular degeneration patients in the daily clinic.

In this work, we developed a wearable system using a commercial stereoscopic head-mounted display. We compared depth first-then contour (df-tc) and contour first-then depth (cf-td) algorithms in terms of images processed per second rate versus the window size and sweep values. Likewise, we performed a comparison of several edge detection methods in the same terms. The developed technical aid was clinically tested. We evaluated the preferred walking speed and the walking speed with and without the devices during three test circuits. For comparative analysis of anxiety levels, we recorded patients’ heart rate data before, during and after the test. The system has proven its potential for enhancing the patients’ mobility and reducing the level of anxiety related to movement activities.

The aim of this review was to provide an update on the potential of cell therapies to restore or replace damaged and/or lost cells in retinal degenerative and optic nerve diseases, describing the available cell sources and the challenges involved in such treatments when these techniques are applied in real clinical practice. Sources include human fetal retinal stem cells, allogenic cadaveric human cells, adult hippocampal neural stem cells, human CNS stem cells, ciliary pigmented epithelial cells, limbal stem cells, retinal progenitor cells (RPCs), human pluripotent stem cells (PSCs) (including both human embryonic stem cells (ESCs) and human induced pluripotent stem cells (iPSCs)) and mesenchymal stem cells (MSCs). Of these, RPCs, PSCs and MSCs have already entered early-stage clinical trials since they can all differentiate into RPE, photoreceptors or ganglion cells, and have demonstrated safety, while showing some indicators of efficacy. Stem/progenitor cell therapies for retinal diseases still have some drawbacks, such as the inhibition of proliferation and/or differentiation in vitro (with the exception of RPE) and the limited long-term survival and functioning of grafts in vivo. Some other issues remain to be solved concerning the clinical translation of cell-based therapy, including (1) the ability to enrich for specific retinal subtypes; (2) cell survival; (3) cell delivery, which may need to incorporate a scaffold to induce correct cell polarization, which increases the size of the retinotomy in surgery and, therefore, the chance of severe complications; (4) the need to induce retinal detachment to perform the subretinal placement of the transplanted cell; and (5) the evaluation of the risk of tumor formation caused by the undifferentiated stem cells and prolific progenitor cells. Despite these challenges, stem/progenitor cells represent the most promising strategy for retinal and optic nerve disease treatment in the near future, and therapeutics assisted by gene techniques, neuroprotective compounds and artificial devices can be applied to fulfil clinical needs.

Producción Científica, Choroidal dystrophies comprise a group of chorioretinal degenerations. However, the different findings observed among these patients make it difficult to establish a correct clinical diagnosis. The objective of this study was to characterize new clinical findings by optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) in these patients. Four family members with a PRPH2 gene mutation (p.Arg195Leu) were included. OCT was performed at the macula, and the thickness of the outer and inner retina, total retina, and choroid was measured. The features of the vascular network were analyzed by OCTA. Patients showed a decreased outer nuclear layer in the avascular area compared with the controls. Two patients presented greater foveal and parafoveal degeneration of the outer retina, whereas the most degenerated area in the rest was the perifovea. Disruption of the third outer band at the foveola is one of the first-altered outer bands. Slow blood flow areas or capillary dropout were main signs in the deep capillary plexus. Microaneurysms were frequently observed in less degenerated retinas. Vascular loops and intraretinal microvascular abnormalities (IRMAs) were present in the superficial plexus. Extensive degeneration of the choriocapillaris was detected. Phenotypic differences were found between patients: two showed central areolar choroidal dystrophy and the rest had extensive chorioretinal atrophy. These signs observed in OCT and OCTA can help to more appropriately define the clinical disease in patients with choroidal dystrophies., Ministerio de Ciencia e Innovación y Fondo Europeo de Desarrollo Regional (FEDER) - (grants PID2019-106230RB-I00, RD16/0008/0001), Ministerio de universidades - (grants FPU16/04114 and FPU18/02964), Instituto de Salud Carlos III - (grant RETICS-FEDER RD16/0008/0016), Asociación Retina Asturias/Cantabria, FARPE-FUNDALUCE y Generalitat Valenciana - (grant IDIFEDER/2017/064)

Background With the emergence of coronary computed tomography (CT) angiography, anomalous aortic origin of a coronary artery (ANOCOR) is more frequently diagnosed. Fractional flow reserve derived from CT (FFRCT) is a noninvasive functional test providing anatomical and functional evaluation of the overall coronary tree. These unique features of anatomical and functional evaluation derived from CT could help for the management of patients with ANOCOR. We aimed to retrospectively evaluate the physiological and clinical impact of FFRCT analysis in the ANOCOR registry population. Methods and Results The ANOCOR registry included patients with ANOCOR detected during invasive coronary angiography or coronary CT angiography between January 2010 and January 2013, with a planned 5‐year follow‐up. We retrospectively performed FFRCT analysis in patients with coronary CT angiography of adequate quality. Follow‐up was performed with a clinical composite end point (cardiac death, myocardial infarction, and unplanned revascularization). We obtained successful FFRCT analyses and 5‐year clinical follow‐up in 54 patients (average age, 60±13 years). Thirty‐eight (70%) patients had conservative treatment, and 16 (30%) patients had coronary revascularization after coronary CT angiography. The presence of an ANOCOR course was associated with a moderate reduction of FFRCT value from 1.0 at the ostium to 0.90±0.10 downstream the ectopic course and 0.82±0.11 distally. No significant difference in FFRCT values was identified between at‐risk and not at‐risk ANOCOR. After a 5‐year follow‐up, only one unplanned percutaneous revascularization was reported. Conclusions The presence of ANOCOR was associated with a moderate hemodynamic decrease of FFRCT values and associated with a low risk of cardiovascular events after a 5‐year follow‐up in this middle‐aged population.

Serious intraocular toxicity cases have been reported worldwide after the use of different perfluorocarbon liquids. The current study reports for the first-time the clinical pictures of cases of acute intraocular toxicity caused by MEROCTANE, a perfluoro-octane commercialized by a Turkish company and distributed in many countries. A series of 18 cases from Chile and Spain was retrospectively analysed. To evaluate the impurity profile, a suspicious MEROCTANE sample (lot OCT.01.2013) was analysed by gas chromatography mass spectrometry and compared with a non-suspicious sample of the same commercial perfluoro-octane (lot OCT 722011). Cytotoxicity was tested following a direct-contact method, taking into consideration the high volatility and hydrophobicity of perfluoro-octane and following the ISO 10993 guideline. Cytotoxicity test showed clear cytotoxic effects of the analysed batch (less than 9% of cell viability). Moreover, chemical analysis demonstrated the presence of many contaminants, some highly toxic (acids and alcohols). Perfluorocarbon liquids are useful tools for intraocular surgery but companies and Agencies of Medical Devices must implement measures that guarantee the safety of these products based on both chemical and cytotoxicity analysis for every batch. Medical staff should be encouraged to report any suspected case to their respective National Agencies.

Debris flows constitute a severe natural hazard in Alpine regions. Studies are performed to understand the event predictability and to identify early warning systems and procedures. These are based both on sensors deployed along the channels or on the amplitude of seismic and infrasound waves radiated by the flow and recorded far away. Despite being very promising, infrasound cannot be used to infer the source characteristics due to the lack of a physical model of the infrasound energy radiated by debris flows. Here the simulation of water flow along a simple channel is presented, experiencing the fall from a dam, performed within the open source simulation code OpenFOAM. The pressure perturbation within the atmosphere produced by the flow is extracted and the infrasound signature of the events as a function of the flow characteristics is defined. Numerical results suggest that infrasound is radiated immediately downstream of the dam with amplitude and period that scale with dam height and water level. Modeled infrasound waveform is interpreted as being produced mostly by waves at the water free surface developing downstream of the dam. Despite the effect of sediments is not considered in this first study and will be implemented in future investigations, numerical results obtained with this simple model are in general agreement with experimental results obtained from array analysis of infrasound data recorded at Illgraben, Switzerland. Results highlight how numerical modeling can provide critical information to define a source mechanism of infrasound energy radiation by debris-flow, that is required also to improve early warning systems.

BACKGROUND: There are almost no available data on retinal involvement after acute exposure to high concentrations mercury and the available reports are on a small number of patients that suffered chronic expposure. The purpose of this paper is to report visual findings in 29 workers exposed to very high concentrations of mercury vapor in a factory in northern Spain in 2012.METHODS: Twenty-nine patients and 16 controls were evaluated in a comparative case series. Fifteen of the 29 workers underwent belated chelation for heavy metal intoxication, only 3 in a prompt way. The mercury levels in blood and urine samples, visual acuity (VA), contrast sensitivity (CS), visual field (VF), color discrimination and optical coherence tomography (OCT) data were recorded. The pattern reversal visual-evoked potentials (PRVEP), full-field and multifocal electroretinography (ffERG/mfERG), pattern electroretinography (PERG), systemic symptoms, presence of erethism, and electromyography (EMG) were also gathered. A descriptive analysis was performed. The evolution of patients who did not undergo chelation (group 1), those who underwent late chelation (group 2), and those with deep VF defects (group 3) were compared with a control group. The correlations between variables also were studied.RESULTS: The VA was affected slightly. The loss of CS in at least one of four spatial frequencies and color vision alterations occurred in 96.5% (n=28) and 44.8% (n=13), respectively, in the entire group. VF alterations were identified in 72.4% (n=21). No morphologic changes were seen in the OCT scans. Latencies over 100 milliseconds and reduced amplitudes of P100 were found in the PRVEP. The ffERG and PERG results suggested that both the outer and inner retinal processes were involved. The mfERG indicated reduced parafoveal retinal function. Twenty-six workers exhibited symptoms of erethism. The EMG showed sensorimotor polyneuropathy and multiple mononeuropathy alterations. Significant negative correlations among blood mercury levels, VA, and ffERG were observed.CONCLUSION: Advanced visual functions were impaired significantly independent of the mercury levels. Delayed chelation was not beneficial. Although neurologic and visual pathway involvement was clearly demonstrated, this study also showed clear functional retinal participation in impaired vision.

This study aims to find out which tool, fundus autofluorescence (FAF) or spectral domain optical coherence tomography (SD-OCT), is more sensitive in detecting retinal pigment epithelium (RPE) demise overlying drusen and can, therefore, help predict geographic atrophy (GA) appearance in Age-Related Macular Degeneration (AMD).A single-site, retrospective, observational, longitudinal study was conducted. Patients with intermediate AMD (iAMD) (large (125 One hundred and thirty-three drusen in 22 eyes of 22 patients were included. Of these, 112 (84.2%) drusen showed choroidal hypertransmission and 21(15.8%) nGA. Early signs of atrophy overlying drusen were found simultaneously on SD-OCT and FAF in 52 cases (39.1%, 95% CI 30.8-47.9%), earliest on FAF in 51 (38.3%, 95% CI 30.0-47.2%) and first on SD-OCT in 30 (22.6%, 95% CI 15.8-30.6%;In iAMD cases in which early atrophy overlying drusen is not detected simultaneously in FAF and SD-OCT, FAF was significantly more sensitive. Nevertheless, a multimodal approach is recommended and required to evaluate these patients.

This study aims to determine the probability of progression of myopic maculopathy according to age.This is a longitudinal observational study of single-center retrospective cohort of Caucasian patients formed by 212 consecutive adults with high myopia. Main outcome measures were age, visual acuity (VA), refractive error (RE), follow-up time, and the macular status assessed at least 5 years apart according to the Meta-Analysis of Pathologic Myopia Study Group. The progression rate was calculated based on per 1000 eyes/year. Multistate models were fitted to identify the predictive factors and to calculate the most probable age of progression onset using the Aalen-Johansen estimator.We studied 220 eyes of 122 Caucasian patients. Mean age was 48.18 ± 14.1, mean follow-up 12.73 ± 5.81 years. One-hundred and fifty-two (69.1%) eyes progressed of category, and 96 (44%) worsened a mean of 0.3 logMAR units during follow-up. The progression rate was 32.21/1000 eyes/year. The probability of progressing increased with age; it was higher in women if there was a family history of myopia, worse VA, higher RE, or wide macular staphyloma. The probability of progressing from category 1 was 0.6 after 70 years of age; from category 2, it was 0.7 after 70 years; and 0.5 from category 3 after 75 years. If choroidal neovascularization (CNV) appeared, this probability exceeded 0.7 between ages 45 and 55 for all categories.The progression rate is lower than in a Japanese series. The vision worsened with disease progression, and the probability of both happening increased after the age of 70-75. If CNV appears, the risk of progression is very high at the age of 45-55.

Retinal degenerations are the leading causes of irreversible visual loss worldwide. Many pathologies included under this umbrella involve progressive degeneration and ultimate loss of the photoreceptor cells, with age-related macular degeneration and inherited and ischemic retinal diseases the most relevant. These diseases greatly impact patients' daily lives, with accompanying marked social and economic consequences. However, the currently available treatments only delay the onset or slow progression of visual impairment, and there are no cures for these photoreceptor diseases. Therefore, new therapeutic strategies are being investigated, such as gene therapy, optogenetics, cell replacement, or cell-based neuroprotection. Specifically, stem cells can secrete neurotrophic, immunomodulatory, and anti-angiogenic factors that potentially protect and preserve retinal cells from neurodegeneration. Further, neuroprotection can be used in different types of retinal degenerative diseases and at different disease stages, unlike other potential therapies. This review summarizes stem cell-based paracrine neuroprotective strategies for photoreceptor degeneration, which are under study in clinical trials, and the latest preclinical studies. Effective retinal neuroprotection could be the next frontier in photoreceptor diseases, and the development of novel neuroprotective strategies will address the unmet therapeutic needs.