Human recombinant nerve growth factor (Cenegermin) in a patient affected by primary congenital glaucoma with neurotrophic keratopathy.

PURPOSE: To report a case of neurotrophic keratopathy (NK) in a patient affected by primary congenital glaucoma (PCG) who undergone glaucoma drainage implant surgery. NK was successfully treated with human recombinant Nerve Growth Factor (Cenegermin) eye drops. CASE REPORT DESCRIPTION: A 46-years-old patient affected by primary congenital glaucoma underwent Ahmed glaucoma valve implantation in the right eye, after several unsuccessful surgeries to control intraocular pressure (IOP) since the age of three. Surgical intervention was performed without complications, and IOP was well-controlled post-operatively. However, 1 month after surgery, he developed NK with stromal ulceration, initially treated with a topical combination of preservative-free artificial tears and antibiotic ointment. As NK did not resolve, a new treatment with Cenegermin 20 µg/ml eye drops, 6 times daily, was started. OUTCOME: NK completely resolved after 8 weeks of Cenegermin treatment, with complete restoration of corneal integrity and improvement of corneal sensitivity and transparency. Visual acuity in the operated eye reverted to the pre-operative value. CONCLUSION: Cenegermin was extremely effective in restoring corneal integrity in this PCG patient with NK.

Evaluation of macular and optic nerve head parameters in amblyopic eyes: An optical coherence tomography study.

PURPOSE: To evaluate morphological differences in retinal nerve fibers layers (RNFL), optic nerve head (ONH), ganglion cell complex (GCC), and macular thickness between amblyopic and normal eyes from spectral domain optical coherence tomography (SD-OCT). METHODS: Of 234 eyes of 117 children, four groups emerged: group A (162 eyes of 81 non-amblyopic subjects); group B (32 fellow eyes of 32 subjects with monolateral amblyopia); group C (32 amblyopic eyes of 32 subjects affected by monolateral amblyopia); group D (8 amblyopic eyes of 4 subjects with bilateral amblyopia). Patients underwent SD-OCT for ONH parameters, RNFL, GCC and macular thickness, retina map, and ONH scan quality index (SQI). Two-sided p values <0.05 were taken as statistically significant. (Analysis: STATA v.13). RESULTS: Parameters with a significant difference between groups (p < 0.005) with their Standard Deviation (SD) are presented: rim area, 2.08 (0.49) mm2 in group A and 1.76 (0.68) mm2 in group C; disk area, 2.43 (0.45) mm2 in group A and 2.02 (0.71) mm2 in group C; central macular thickness, 250.99 (19.74) µm in group A and 267.16 (23.52) µm in group C; nerve fiber ONH SQI, 62.82 (13.15) in group A, 51.26 (15.55) in group C, 48.29 (14.37) in group D; retina map SQI, 63.34 (10.34) in group A and 57.34 (9.84) in group C. For other parameters no significant difference was observed (p > 0.005). CONCLUSIONS: Amblyopia may influence optic nerve morphology, central macular thickness, and OCT scan quality. RNFL and GCC are not affected by monolateral amblyopia.

A Comparison of Hyper-Reflective Retinal Spot Counts in Optical Coherence Tomography Images from Glaucomatous and Healthy Eyes.

PURPOSE: To compare the number of hyper-reflective retinal spots (HRS) in optical coherence tomography (OCT) images of healthy controls and patients affected with primary open angle glaucoma (POAG). METHODS: Thirty patients affected with POAG and 34 healthy controls were recruited and underwent raster OCT examination of the macular region. Among the acquired B-scans, the one with the lowest foveal thickness was selected, and a central area of 3000 µm was defined (region of interest, ROI), in order to identify HRS. HRS were defined as small point-like hyper-reflective elements, detectable at the visual inspection of the OCT image. HRS were independently counted by two investigators in the ROI of each OCT scan. RESULTS: Inter-rater agreement for HRS counting was good to excellent (ICC = 0.96, 95% CI: 0.83-0.99). More HRS were found in the OCT images from glaucoma patients, in comparison with healthy controls (average value: 90.5 ± 13.02 and 74.72 ± 11.35, for glaucoma and healthy subjects, respectively; p < 0.01). Significant correlations between the average number of HRS and visual field mean deviation (MD, p = 0.01) and pattern standard deviation (PSD, p < 0.01) were found. CONCLUSIONS: OCT images from glaucoma patients showed a higher number of HRS when compared with healthy controls. As HRS have been hypothesized to be a sign of neuroinflammation, these results may support the role of neuroinflammation in glaucoma etiopathogenesis.

Single-Pass Mikrokeratome and Anterior Chamber Pressurizer for the Ultrathin Descemet-Stripping Automated Endothelial Keratoplasty Graft Preparation.

PURPOSE: To compare the reliability of microkeratome dissection with the anterior chamber pressurizer (ACP) system versus conventional pressurization for ultrathin Descemet-stripping automated endothelial keratoplasty (UT-DSAEK) graft preparation. METHODS: A retrospective review of a consecutive series of dissected donor corneas processed at Pavia Eye Bank for UT-DSAEK surgery was performed. Grafts were prepared through single-pass microkeratome dissection with artificial anterior chamber internal pressure regulation through either ACP or the conventional method using a water column with tube clamp. The target central graft thickness (CGT) was ≤100 µm. Cutting predictability was determined as the difference between the microkeratome head size and the thickness actually removed. Graft regularity was investigated as central-to-peripheral thickness increase, central-to-peripheral (CP) ratio, and graft thickness uniformity. Thickness was measured with anterior segment optical coherence tomography (horizontal and vertical meridians). RESULTS: Of the 265 UT-DSAEK grafts, ACP achieved the target "CGT ≤ 100 µm" in 87 of 120 (72.5%), whereas the conventional technique achieved the same in 85 of 145 (58.6%) (P = 0.018). ACP predictability was -3.9 µm (SD: 2.3), whereas predictability of the conventional technique was -54.6 µm (SD: 3.7) (P < 0.001). Thickness increased similarly (P = 0.212); CP ratio was better with ACP for only 2 mm diameter (P = 0.001); graft thickness uniformity was comparable (P > 0.05). CONCLUSIONS: Compared with conventional pressurization, ACP improved microkeratome-assisted preparation reliability of UT-DSAEK grafts, achieving CGT ≤ 100 µm with significantly higher frequency (P = 0.018) and predictability (P < 0.001). ACP improved CP ratio only at 2 mm (P = 0.001); for other graft thickness, the 2 methods proved equivalent.

Glaucoma and neuroinflammation: An overview.

Glaucoma is an optic neuropathy characterized by well-defined optic disc morphological changes (i.e., cup enlargement, neuroretinal border thinning, and notching, papillary vessel modifications) consequent to retinal ganglion cell loss, axonal degeneration, and lamina cribrosa remodeling. These modifications tend to be progressive and are the main cause of functional damage in glaucoma. Despite the latest findings about the pathophysiology of the disease, the exact trigger mechanisms and the mechanism of degeneration of retinal ganglion cells and their axons have not been completely elucidated. Neuroinflammation may play a role in both the development and the progression of the disease as a result of its effects on retinal environment and retinal ganglion cells. We summarize the latest findings about neuroinflammation in glaucoma and examine the connection between risk factors, neuroinflammation, and retinal ganglion cell degeneration.

Identification of SARS-CoV-2 RNA in the conjunctival swab of an Italian pediatric patient affected with COVID-19: A case report.

INTRODUCTION: To report a case of identification of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) RNA in ocular specimen in a pediatric patient affected with Coronavirus disease 2019 (COVID-19) with no signs of ocular involvement. CASE DESCRIPTION: A 11-year old male patient with confirmed COVID-19 infection was hospitalized at the Pediatric Clinic Clinic of the IRCCS Foundation and Hospital San Matteo, Pavia, Italy. Three days after hospital admission, because of the patient complaining very mild ocular symptoms, an ophthalmological evaluation was performed. No signs related to conjunctivitis or keratitis were found but a conjunctival swab was collected as well, based on patient's medical history. The specific SARS-CoV-2 reverse transcription PCR (RT-PCR) was performed, unearthing the presence of viral RNA from the swab. On day 25 from hospitalization, the conjunctival swab was repeated, giving negative result. CONCLUSIONS: This is the first report of the identification of SARS-CoV-2 RNA in ocular specimen in a pediatric patient without signs of ocular involvement. However, despite the transmission through tears is theoretically possible, it is still unclear whether this could be considered as an important route for the spread of SARS-CoV-2.

Anterior Chamber Angle Assessment Techniques: A Review.

Assessment of the anterior chamber angle (ACA) is an essential part of the ophthalmological examination. It is intrinsically related to the diagnosis and treatment of glaucoma and has a role in its prevention. Although slit-lamp gonioscopy is considered the gold-standard technique for ACA evaluation, its poor reproducibility and the long learning curve are well-known shortcomings. Several new imaging techniques for angle evaluation have been developed in the recent years. However, whether these instruments may replace or not gonioscopy in everyday clinical practice remains unclear. This review summarizes the last findings in ACA evaluation, focusing on new instruments and their application to the clinical practice. Special attention will be given to the comparison between these new techniques and traditional slit-lamp gonioscopy. Whereas ultrasound biomicroscopy and anterior segment optical coherence tomography provide quantitative measurements of the anterior segment's structures, new gonio-photographic systems allow for a qualitative assessment of angle findings, similarly to gonioscopy. Recently developed deep learning algorithms provide an automated classification of angle images, aiding physicians in taking faster and more efficient decisions. Despite new imaging techniques made analysis of the ACA more objective and practical, the ideal method for ACA evaluation has still to be determined.

Astronaut EVA exposure estimates from CAD model spacesuit geometry.

Ongoing assembly and maintenance activities at the International Space Station (ISS) require much more extravehicular activity (EVA) than did the earlier U.S. Space Shuttle missions. It is thus desirable to determine and analyze, and possibly foresee, as accurately as possible what radiation exposures crew members involved in EVAs will experience in order to minimize risks and to establish exposure limits that must not to be exceeded. A detailed CAD model of the U.S. Space Shuttle EVA Spacesuit, developed at NASA Langley Research Center (LaRC), is used to represent the directional shielding of an astronaut; it has detailed helmet and backpack structures, hard upper torso, and multilayer space suit fabric material. The NASA Computerized Anatomical Male and Female (CAM and CAF) models are used in conjunction with the space suit CAD model for dose evaluation within the human body. The particle environments are taken from the orbit-averaged NASA AP8 and AE8 models at solar cycle maxima and minima. The transport of energetic particles through space suit materials and body tissue is calculated by using the NASA LaRC HZETRN code for hadrons and a recently developed deterministic transport code, ELTRN, for electrons. The doses within the CAM and CAF models are determined from energy deposition at given target points along 968 directional rays convergent on the points and are evaluated for several points on the skin and within the body. Dosimetric quantities include contributions from primary protons, light ions, and electrons, as well as from secondary brehmsstrahlung and target fragments. Directional dose patterns are displayed as rays and on spherical surfaces by the use of a color relative intensity representation.

Lunar lava tube radiation safety analysis.

For many years it has been suggested that lava tubes on the Moon could provide an ideal location for a manned lunar base, by providing shelter from various natural hazards, such as cosmic radiation, meteorites, micrometeoroids, and impact crater ejecta, and also providing a natural environmental control, with a nearly constant temperature, unlike that of the lunar surface showing extreme variation in its diurnal cycle. An analysis of radiation safety issues on lunar lava tubes has been performed by considering radiation from galactic cosmic rays (GCR) and Solar Particle Events (SPE) interacting with the lunar surface, modeled as a regolith layer and rock. The chemical composition has been chosen as typical of the lunar regions where the largest number of lava tube candidates are found. Particles have been transported all through the regolith and the rock, and received particles flux and doses have been calculated. The radiation safety of lunar lava tubes environments has been demonstrated.

Implementation of Gy-Eq for deterministic effects limitation in shield design.

The NCRP has recently defined RBE values and a new quantity (Gy-Eq) for use in estimation of deterministic effects in space shielding and operations. The NCRP's RBE for neutrons is left ambiguous and not fully defined. In the present report we will suggest a complete definition of neutron RBE consistent with the NCRP recommendations and evaluate attenuation properties of deterministic effects (Gy-Eq) in comparison with other dosimetric quantities.

Advances in space radiation shielding codes.

Early space radiation shield code development relied on Monte Carlo methods and made important contributions to the space program. Monte Carlo methods have resorted to restricted one-dimensional problems leading to imperfect representation of appropriate boundary conditions. Even so, intensive computational requirements resulted and shield evaluation was made near the end of the design process. Resolving shielding issues usually had a negative impact on the design. Improved spacecraft shield design requires early entry of radiation constraints into the design process to maximize performance and minimize costs. As a result, we have been investigating high-speed computational procedures to allow shield analysis from the preliminary concept to the final design. For the last few decades, we have pursued deterministic solutions of the Boltzmann equation allowing field mapping within the International Space Station (ISS) in tens of minutes using standard Finite Element Method (FEM) geometry common to engineering design methods. A single ray trace in such geometry requires 14 milliseconds and limits application of Monte Carlo methods to such engineering models. A potential means of improving the Monte Carlo efficiency in coupling to spacecraft geometry is given.

A retrospective cohort mortality study of Italian commercial airline cockpit crew and cabin attendants, 1965-96.

A retrospective cohort mortality study was conducted among Italian commercial flight personnel for the period 1965-1996. The cohort was composed of 3,022 male cockpit crew members and 3,418 male and 3,428 female cabin attendants. Cause-specific standardized mortality ratios (SMRs) and exact 95% confidence intervals (CIs) were calculated as estimates of the relative risk. Mortality from all cancers was less than expected for all categories (SMRs of 0.58 for male cockpit crew, 0.67 for male cabin attendants, and 0.90 for female cabin attendants). Among male flight personnel, the SMR for leukemia was somewhat elevated (SMR 1.73; 95% CI: 0.75-3.41) based on eight deaths, with a positive trend by length of employment (p = 0.046). Additionally, an excess of death by suicide was seen among female cabin attendants (SMR 3.38; 95% CI: 1.24-7.35). Other Italian studies of flight personnel are under way, including a detailed assessment of cosmic radiation exposure and investigations of non-radiation occupational risk factors and prevalence of nonfatal outcomes.

Preliminary validation of computational procedures for a new atmospheric ionizing radiation (AIR) model.

A new computational procedure to determine particle fluxes in the Earth's atmosphere is presented. The primary cosmic ray spectrum has been modeled through an analysis of simultaneous proton and helium measurements made on high altitude balloon flights and spacecraft. An improved global fit to the data was achieved through applying a unique technique utilizing the Fokker-Plank equation with a non-linear rigidity-dependent diffusion coefficient. The propagation of primary particles through the Earth's atmosphere is calculated with a three-dimensional Monte Carlo transport program called FLUKA. Primary protons and helium nuclei (alphas) are generated within the rigidity range of 0.5 GV-20 TV uniform in cos2 theta. For a given location, primaries above the effective cutoff rigidity are transported through the atmosphere. Alpha particles are initially transported with a separate package called HEAVY to simulate fragmentation. This package interfaces with FLUKA to provide interaction starting points for each nucleon originating from a helium nucleus. Results from this calculation are presented and compared to measurements.

Chemometric investigation of the efficiency of different TiO(2)-based catalysts as principal components of TOC photochemical sensors under development.

There is an increasing demand for measurement of organic carbon in solutions both in industry and in environmental research for the purpose of continuous water-quality monitoring. Practically all the methods used are based on a catalytic system in which metal oxides play a major role. The development of a new TOC/DOC measurement system, in our work, uses a mixed anatase-rutile form of TiO(2 )as catalyst of the mineralisation process, and direct measurement of the CO(2) produced, by a gaseous diffusion electrode. The entire research is based on heterogeneous catalysis using an immobilised catalyst, which can offer considerable advantages over other methods of catalysis. Four different catalytic systems were analysed. Three involved thermal immobilisation of TiO(2) on glass supports (glass spheres and glassy particulates) or on an Al metal grid. One further system consisted of direct oxidation of a Ti grid at high temperatures. The system was illuminated using a 350 nm UV source (350 mW cm(-2)) contained in a home-made measurement cell. Five molecules-malic acid, pentachlorophenol, sodium dodecylsulfate, hydroquinone, and citric acid-which were deemed to be representative and had been investigated in several previous studies, were used as photodegradation targets. However, it was not possible to obtain a direct expression of "catalytic efficiency" simply by reading the data obtained, nor any indirect molecular "recalcitrancy" scale. Chemometric analysis, by principal components analysis, allows the five used catalytic systems to be easily compared each other and a single PC component is able to perform classification.

Estimation and projections of cancer prevalence from cancer registry data.

A method, PIAMOD (Prevalence, Incidence, Analysis MODel), which allows the estimation and projection of cancer prevalence patterns by using cancer registry incidence and survival data is presented. As a first step the method involves the fit of incidence data by an age, period and cohort model to derive incidence projections. Prevalence is then estimated from modelled incidence and survival estimates. Cancer mortality is derived as a third step from modelled incidence, prevalence and survival. An application to female breast cancer is given for the Connecticut State by using data from the Connecticut Tumor Registry (CTR), 1973-1993. The age, period and cohort model fitted incidence quite well and allowed us to derive long-term projections up to 2030. Patients' survival was also projected to future years according to a scenario approach based on two extreme hypotheses: steady, that is, no more improvements after 1993 (conservative), and continuously improving at the same rate as during the observation period. Age-standardized estimated incidence shows a changing trend around the year 2005, when it starts decreasing. Age-standardized prevalence is expected to increase and change trend at a later date. Breast cancer mortality is projected as decreasing, as the combined result of no further increase in incidence and improving cancer patients' survival. An easy-to-use PIAMOD software package, on which work is in progress, will be made available to individual cancer registries and/or health planning institutions or authorities once it is developed. The use of the PIAMOD method for cancer registries will allow them to provide results of paramount importance for the whole community involved in the assessment of future disease burden scenarios in an evolving society.