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At least 19 records

An Ophthalmologic Summit for On-Orbit Care

Ophthalmologic issues are a source of concern for NASA flight surgeons, due to the remote nature of the space station as well as the microg ravity environment. Methods: A panel of external consultants was conv ened to evaluate the adequacy of the current in-flight medical system for the diagnosis and treatment of ophthalmologic issues. Participants were acknowledged experts in their field who also had experience in operational medicine. Results: Nine extramural experts provided assi stance, and six of them participated in a face to face meeting held a t NASA-Johnson Space Center. Changes were recommended for the space s tation pharmacopoeia, and diagnostic, therapeutic, and deorbit criteria protocols for a variety of ocular conditions were developed. Discus sion: The results of the panel provide an evidence based approach to the diagnosis and care of ophthalmologic conditions on the International Space Station

Bacal, Kira↗

Late ophthalmological complications after total body irradiation in non-human primates

PURPOSE: To investigate the long-term effects of total body irradiation (TBI) on the incidence and time course of ocular complications. MATERIALS AND METHODS: Rhesus monkeys treated with TBI photon doses up to 8.5 Gy and proton doses up to 7.5 Gy were studied at intervals up to 25 years post-irradiation. They were compared with control groups with a similar age distribution. Cataract formation and ocular fundus lesions were scored according to a standardized protocol. Fluorescein angiography and histopathology was performed in selected animals. RESULTS: Cataract formation occurred after a latent period of 3-5 years. Significant cataract induction was observed for photon-doses of 8 and 8.5 Gy and beyond 20 years after proton irradiation. The severity of the lesions represents significant impairment of vision and would require cataract surgery if similar results occurred in human bone marrow transplant patients. Fluorescein angiography demonstrated a normal pattern of retinal vessels in 13 out of 14 animals (93%) from the irradiated group and in eight out of nine animals (89%) from the control group. No additional lesions apart from age-related degenerative changes could be demonstrated. Histological evaluation revealed no radiation-associated vasculopathy. CONCLUSIONS: Radiation alone for doses up to 8.5 Gy of photons does not carry a potential risk for fundus pathology, whereas clinically important cataract induction should be anticipated within 5 years after photon doses of 8.0 and 8.5 Gy and proton doses in excess of 2.5 Gy.

NASA Discipline Radiation Health↗

Ocular Outcomes Comparison Between 14- and 70-day Head-down Tilt Bed Rest

INTRODUCTION: Ophthalmological changes, including optic disc edema with optic nerve sheath distension, posterior globe flattening with hyperopic shift, choroidal folds and cotton wool spots have been detected in some astronauts involved in long-duration spaceflights. (sup 1) It is hypothesized that elevated intracranial pressure resulting from microgravity-induced cephalad fluid shifts may be responsible for most of these findings. Head-down tilt bed rest (HTDBR) is a ground-based microgravity analog which also produces cephalad fluid shifts. It is conceivable that prolonged HDTBR exposure may induce ocular changes similar to those experienced in microgravity. Therefore, the purpose of the present study was to compare structural and functional ocular outcomes between 14- and 70-day HDTBR in healthy human subjects. It is hypothesized that 70-d HDTBR induced ocular changes of greater magnitude as compared to 14-d HDTBR. METHODS: Two HDTBR studies were conducted at the NASA Flight Analogs Research Unit, located at The University of Texas Medical Branch at Galveston, TX. Identical NASA standard screening procedures and BR conditions (e.g., strict sleep-wake cycle, standardized diet, continuous video monitoring) were implemented in both studies. Participants spent 14 and/or 70 consecutive days in a 6deg HDT position and did not engage in exercise. Subjects received weekly ocular examinations before, during, and after HDTBR. Ocular testing included: distance and near best-corrected visual acuity (BCVA), cycloplegic refraction, intraocular pressure (IOP) measurement, color vision, red dot test, modified Amsler grid test, confrontational visual field, color fundus photography and Spectral-domain OCT scans of the macula and the optic disc. Pre/post HDTBR differences between the two studies will be evaluated for BCVA, spherical equivalent, IOP, retinal nerve fiber layer (RNFL) thickness and macular OCT parameters. RESULTS: 16 (12 males and 4 females) and 6 (5 males and 1 female) subjects participated in the 14 and 70-day HDTBR studies, respectively. One subject participated in both studies. The demographic and ophthalmological characteristics of the 14-day HDTBR study have been presented elsewhere.2 In the 70- day study, subjects age averaged 39.5 +/- 7.8 years; pre- and post-HDTBR Goldmann IOP were, on average, 15.4 and 14.6 mmHg in the right eye, and 15.3 and 14.4 mmHg in the left eye, respectively; preand post-HDTBR Spectralis OCT (Heidelberg Engineering, GmbH, Heidelberg, Germany) average RNFL thickness were 103.8 and 106 μm in the right eye, and 103 and 104.3 μm in the left eye, respectively. In both studies, color vision, red dot test, modified Amsler grid test and confrontational visual field were within normal limits at all time points; no changes were detected on stereoscopic color optic disc photography. For the above outcomes, preliminary results of the pre/post HDTBR differences between the two studies will be presented at the 2015 Human Research Program Investigators' Workshop. CONCLUSIONS: Although 14-day HDTBR did not seem to induce clinically relevant ocular changes, (sup 2) a systematic evaluation and comparison with the 70-day HDTBR study results will elucidate whether the magnitude of ocular structural and functional changes is affected by the time spent in the recumbent position. Further research will also address the effects of integrated resistance and aerobic training during HDTBR on the ocular outcomes. REFERENCES: 1. Mader TH et al. Optic disc edema, globe flattening, choroidal folds, and hyperopic shifts observed in astronauts after long-duration space flight. Ophthalmology. 2011;118(10):2058-69. 2. Taibbi G et al. Ocular outcomes evaluation in a 14-day head-down bed rest study. Aviat Space Environ Med. 2014;85(10):983-92.

Cromwell, R.L.↗

Novel compound heterozygous CPLANE1 variants identified in a Chinese family with Joubert syndrome

Abstract Joubert syndrome (JS) and JS‐related disorders (JSRD) are a group of neurodevelopmental diseases that share the “molar tooth sign” on axial brain magnetic resonance imaging (MRI), accompanied by cerebellar vermis hypoplasia, ataxia, hypotonia, and developmental delay. To identify variants responsible for the clinical symptoms of a Chinese family with JS and to explore the genotype–phenotype associations, we conducted a series of clinical examinations, including blood tests, brain MRI scans, ultrasound imaging, and ophthalmologic examination. Genomic DNA was extracted from the peripheral blood of the six‐person family, and the pathogenic variants were detected by whole‐exome sequencing (WES) and verified by Sanger sequencing. WES revealed two novel compound heterozygous variants in CPLANE1 : c.1270C>T (p.Arg424*) in exon 10 and c.8901C>A (p.Tyr2967*) in exon 48 of one child, inherited from each parent. Both variants were absent in ethnically matched Chinese control individuals and were either absent or present at very low frequencies in public databases, suggesting that these variants could be the pathogenic triggers of the JS phenotype. Notably, these CPLANE1 sequence variants were related to the pathogenesis of autosomal recessive JS in this study. The newly discovered variants expand the mutation spectrum of CPLANE1 , which assists in understanding the molecular mechanism underlying JS and improving the recognition of genetic counseling, particularly for families with a history of autosomal recessive JS.

Zhang, Cheng↗

Younger facial looks are associate with a lower likelihood of several age-related morbidities in the middle-aged to elderly

Abstract Background Looking older for one’s chronological age is associated with a higher mortality rate. Yet it remains unclear how perceived facial age relates to morbidity and the degree to which facial ageing reflects systemic ageing of the human body. Objectives To investigate the association between ΔPA and age-related morbidities of different organ systems, where ΔPA represents the difference between perceived age (PA) and chronological age. Methods We performed a cross-sectional analysis on data from the Rotterdam Study, a population-based cohort study in the Netherlands. High-resolution facial photographs of 2679 men and women aged 51.5–87.8 years of European descent were used to assess PA. PA was estimated and scored in 5-year categories using these photographs by a panel of men and women who were blinded for chronological age and medical history. A linear mixed model was used to generate the mean PAs. The difference between the mean PA and chronological age was calculated (ΔPA), where a higher (positive) ΔPA means that the person looks younger for their age and a lower (negative) ΔPA that the person looks older. ΔPA was tested as a continuous variable for association with ageing-related morbidities including cardiovascular, pulmonary, ophthalmological, neurocognitive, renal, skeletal and auditory morbidities in separate regression analyses, adjusted for age and sex (model 1) and additionally for body mass index, smoking and sun exposure (model 2). Results We observed 5-year higher ΔPA (i.e. looking younger by 5 years for one’s age) to be associated with less osteoporosis [odds ratio (OR) 0.76, 95% confidence interval (CI) 0.62–0.93], less chronic obstructive pulmonary disease (OR 0.85, 95% CI 0.77–0.95), less age-related hearing loss (model 2; B = −0.76, 95% CI −1.35 to −0.17) and fewer cataracts (OR 0.84, 95% CI 0.73–0.97), but with better global cognitive functioning (g-factor; model 2; B = 0.07, 95% CI 0.04–0.10). Conclusions PA is associated with multiple morbidities and better cognitive function, suggesting that systemic ageing and cognitive ageing are, to an extent, externally visible in the human face.

Mekić, Selma↗

Optical coherence tomography imaging of plant root growth in soil

Complex interactions between roots and soil provide the nutrients and physical support required for robust plant growth. Yet, visualizing the root-soil interface is challenged by soil’s opaque scattering characteristics. In this paper, we describe methods for using optical coherence tomography (OCT) to provide non-destructive 3D and cross-sectional root imaging not available with traditional bright field microscopy. OCT is regularly used for bioimaging, especially in ophthalmology where it can detect retinal abnormalities. Prior use of OCT in plant biology has focused on surface defects of above ground tissues, predominantly in food crops. Our results show OCT is also viable for detailed, in situ study of living plant roots.

59 BASIC BIOLOGICAL SCIENCES↗

Lasers in biology and medicine

Laser applications in biology and medicine covering surgery, ophthalmology, microorganisms, viruses, tissue culture, tumor eradication, radiation hazards, etc

Fine, S.↗

Intraocular pressure reduction and regulation

System designed to reduce intraocular pressure hydraulically to any level desired by physician over set time and in controlled manner has number of uses in ophthalmology. Device may be most immediately useful in treatment of glaucoma.

Baehr, E. F.↗

Test and evaluation of the 2.4-micron photorefractor ocular screening system

An improved 2.4-m photorefractor ocular screening system was tested and evaluated. The photorefractor system works on the principal of obtaining a colored photograph of both human eyes; and, by analysis of the retinal reflex images, certain ocular defects can be detected such a refractive error, strabismus, and lens obstructions. The 2.4-m photorefractory system uses a 35-mm camera with a telephoto lens and an electronic flash attachment. Retinal reflex images obtained from the new 2.4-m system are significantly improved over earlier systems in image quality. Other features were also improved, notably portability and reduction in mass. A total of 706 school age children were photorefracted, 211 learning disabled and 495 middle school students. The total students having abnormal retinal reflexes were 156 or 22 percent, and 133 or 85 percent of the abnormal had refractive error indicated. Ophthalmological examination was performed on 60 of these students and refractive error was verified in 57 or 95 percent of those examined. The new 2.4-m system has a NASA patent pending and is authorized by the FDA. It provides a reliable means of rapidly screening the eyes of children and young adults for vision problems. It is especially useful for infants and other non-communicative children who cannot be screened by the more conventional methods such as the familiar E chart.

Richardson, J. R.↗

Clinical applications of computerized thermography

Computerized or digital, thermography is a rapidly growing diagnostic imaging modality. It has superseded contact thermography and analog imaging thermography which do not allow effective quantization. Medical applications of digital thermography can be classified in two groups: static and dynamic imaging. They can also be classified into macro thermography (resolution greater than 1 mm) and micro thermography (resolution less than 100 microns). Both modalities allow a thermal resolution of 0.1 C. The diagnostic power of images produced by any of these modalities can be augmented by the use of digital image enhancement and image recognition procedures. Computerized thermography has been applied in neurology, cardiovascular and plastic surgery, rehabilitation and sports medicine, psychiatry, dermatology and ophthalmology. Examples of these applications are shown and their scope and limitations are discussed.

Anbar, Michael↗

High power diode lasers for solid-state laser pumps

The development and commercial application of high power diode laser arrays for use as solid-state laser pumps is described. Such solid-state laser pumps are significantly more efficient and reliable than conventional flash-lamps. This paper describes the design and fabrication of diode lasers emitting in the 780 - 900 nm spectral region, and discusses their performance and reliability. Typical measured performance parameters include electrical-to-optical power conversion efficiencies of 50 percent, narrow-band spectral emission of 2 to 3 nm FWHM, pulsed output power levels of 50 watts/bar with reliability values of over 2 billion shots to date (tests to be terminated after 10 billion shots), and reliable operation to pulse lengths of 1 ms. Pulse lengths up to 5 ms have been demonstrated at derated power levels, and CW performance at various power levels has been evaluated in a 'bar-in-groove' laser package. These high-power 1-cm stacked-bar arrays are now being manufactured for OEM use. Individual diode laser bars, ready for package-mounting by OEM customers, are being sold as commodity items. Commercial and medical applications of these laser arrays include solid-state laser pumping for metal-working, cutting, industrial measurement and control, ranging, wind-shear/atmospheric turbulence detection, X-ray generation, materials surface cleaning, microsurgery, ophthalmology, dermatology, and dental procedures.

Linden, Kurt J.↗

Three-Dimensional Optical Coherence Tomography

Three-dimensional (3D) optical coherence tomography (OCT) is an advanced method of noninvasive infrared imaging of tissues in depth. Heretofore, commercial OCT systems for 3D imaging have been designed principally for external ophthalmological examination. As explained below, such systems have been based on a one-dimensional OCT principle, and in the operation of such a system, 3D imaging is accomplished partly by means of a combination of electronic scanning along the optical (Z) axis and mechanical scanning along the two axes (X and Y) orthogonal to the optical axis. In 3D OCT, 3D imaging involves a form of electronic scanning (without mechanical scanning) along all three axes. Consequently, the need for mechanical adjustment is minimal and the mechanism used to position the OCT probe can be correspondingly more compact. A 3D OCT system also includes a probe of improved design and utilizes advanced signal- processing techniques. Improvements in performance over prior OCT systems include finer resolution, greater speed, and greater depth of field.

Gutin, Mikhail↗

A Novel Method for Quantifying Helmeted Field of View of a Spacesuit - And What It Means for Constellation

Field of view has always been a design feature paramount to helmet design, and in particular spacesuit design, where the helmet must provide an adequate field of view for a large range of activities, environments, and body positions. Historically, suited field of view has been evaluated either qualitatively in parallel with design or quantitatively using various test methods and protocols. As such, oftentimes legacy suit field of view information is either ambiguous for lack of supporting data or contradictory to other field of view tests performed with different subjects and test methods. This paper serves to document a new field of view testing method that is more reliable and repeatable than its predecessors. It borrows heavily from standard ophthalmologic field of vision tests such as the Goldmann kinetic perimetry test, but is designed specifically for evaluating field of view of a spacesuit helmet. In this test, four suits utilizing three different helmet designs were tested for field of view. Not only do these tests provide more reliable field of view data for legacy and prototype helmet designs, they also provide insight into how helmet design impacts field of view and what this means for the Constellation Project spacesuit helmet, which must meet stringent field of view requirements that are more generous to the crewmember than legacy designs.

McFarland, Shane M.↗

Fluid Shifts Before, During, and After Prolonged Space Flight and their Association with Intracranial Pressure and Visual Impairment

With the conclusion of the Space Shuttle program, NASA is focusing on long-duration missions on the International Space Station (ISS) and future exploration-class missions beyond low Earth orbit. Visual acuity changes observed in Space Shuttle crewmembers after their short-duration missions were largely transient, but more than 30% of ISS astronauts experience more profound changes in vision, some with objective structural and functional findings such as papilledema and choroidal folds on ophthalmologic examination. Globe flattening, optic nerve sheath dilatation, optic nerve tortuosity, and other findings have been noted in imaging studies. This pattern is referred to as visual impairment and intracranial pressure (VIIP) syndrome. The VIIP signs and symptoms, as well as postflight lumbar puncture data, suggest that elevated intracranial pressure (ICP) is associated with the space flight-induced cephalad fluid shifts, but this hypothesis has not been systematically tested. The purpose of this study is to objectively characterize the fluid distribution and compartmentalization associated with long-duration space flight, and to correlate the findings with vision changes and other elements of the VIIP syndrome. We also seek to determine whether the magnitude of fluid shifts during space flight, as well as the VIIP-related effects of those shifts, can be predicted by crewmember baseline data and responses to acute hemodynamic manipulations (such as head-down tilt tests) obtained before flight. Lastly, we will evaluate the patterns of fluid distribution in astronaut subjects on the ISS during the use of lower body negative pressure (LBNP) and respiratory maneuvers to characterize and explain general and individual responses during space flight.

Stenger, M.↗

Comparison of Structural and Functional Ocular Outcomes Between 14- and 70 Day Bed Rest

Purpose: To compare structural and functional ocular outcomes in healthy human subjects undergoing 14- and/or 70-day head-down-tilt bed rest (HDTBR). We hypothesized the amount of HDTBR-induced ocular changes be affected by the HDTBR duration. Methods: The studies were conducted at the NASA Flight Analogs Research Unit, The University of Texas Medical Branch at Galveston, Galveston, TX. Participants were selected using NASA standard screening procedures. Standardized NASA screening procedures and bed rest conditions (e.g., strict sleep-wake cycle, standardized diet, continuous video monitoring) were implemented in both studies. Participants maintained a 6deg HDTBR position for 14 and/or 70 consecutive days and did not engage in exercise. Weekly ophthalmological examinations were conducted in the sitting (pre/post-bed rest only) and HDT positions. Ocular outcomes of interest included: near best-corrected visual acuity (BCVA); spherical equivalent, as determined by cycloplegic autorefraction; Goldmann applanation tonometry and iCare (Icare Finland Oy, Espoo, Finland) intraocular pressure (IOP) measurement; color vision; red dot test; modified Amsler grid test; confrontational visual field; stereoscopic color fundus photography; Spectralis OCT (Heidelberg Engineering, GmbH, Heidelberg, Germany) retinal nerve fiber layer thickness (RNFLT), peripapillary and macular retinal thicknesses. Mixed-effects linear models were used to compare pre- and post-HDTBR observations between 14- and 70-day HDTBR for our continuously scaled outcomes.

Cromwell, R. L.↗

One-Carbon Metabolism and SANS 2022 Update

Spaceflight Associated Neuro-ocular Syndrome, or SANS, affects a subset of astronauts (1, 2), and biochemical evidence has documented differences in those astronauts (3). Specifically, they had higher circulating concentrations of metabolites of the one-carbon metabolic pathway (1C), including homocysteine, and these concentrations were higher before flight (3). After ruling out many potential confounding factors in these otherwise healthy individuals (e.g., sex, kidney function, vitamin status, coffee consumption), a study of genetics was warranted. In an initial pilot effort, we documented a genetic predisposition to develop ophthalmic changes after long-duration space flight (4). That is, from a limited study of 5 single-nucleotide polymorphisms (SNPs), we found that the G allele for the MTRR A66G SNP was associated with a greater risk of choroidal folds and cotton-wool spots after flight, and the C allele for SHMT1 C1420T was protective against optic disc edema (4). These data provide a potential pathway for understanding why some individuals develop SANS, while others do not. The initial pilot study of 5 SNPs yielded striking findings, but the 1C pathway is far more complex. An effort was undertaken to examine more than 500 1C SNPs to see if a broader examination could help illuminate this association. That work is ongoing. The astronaut findings led us to advocate for the inclusion of 1C pathway genetic and biochemistry testing on other SANS-related projects, noting that genetics might help identify responders, non-responders, or outliers. The first such effort yielded evidence of an association of specific forms of the MTRR and SHMT-1 SNPs and vitamin B12 status with end-tidal CO2 after acute carbon dioxide exposure (5). The second such effort led to the identification that individuals exposed to strict head-down tilt and CO2 for 30-d who developed optic disc edema also had risk alleles for the two SNPs described above (6). Additionally, we identified a clinical population with many characteristics either attributed or purported to be involved in the ocular changes seen in affected astronauts: women with polycystic ovary syndrome (PCOS). PCOS is a condition of androgen excess and anovulatory menstrual cycles. The shared characteristics and clinical findings between SANS and PCOS generally include higher circulating homocysteine concentrations, increased retinal nerve fiber layer thickness, increased androgen concentrations (or responses), and altered carbohydrate metabolism. To our knowledge, no study has examined whether women with PCOS have asymptomatic ophthalmic anomalies observed in astronauts with SANS. While researchers have evaluated the one-carbon metabolism pathway polymorphisms of PCOS patients, and initial studies show an association with certain one-carbon polymorphisms, none have looked at the set of SNPs identified in our studies that are associated with ophthalmic changes in astronauts. Accordingly, we designed a study to evaluate the association of one-carbon pathway SNPs and ophthalmic findings in patients with PCOS and/or IIH compared to controls. Subjects provided blood samples for vitamin and one carbon biochemistry analyses, an extensive analysis of >500 SNPs associated with one carbon metabolism and had eye examinations and ocular imaging. Data analysis are underway. The data collected to date have shown associations between one carbon pathway biochemistry and genetics and incidence of SANS. The mechanisms for SANS has yet to be identified, although many hypotheses exist. Based on our data, we have developed (8, 9) and expanded (6) a multi-hit hypothesis for how these seemingly disparate findings could be linked. While intriguing, the hypothesis represents the starting point for further research. We aim to clarify the relationship between B-vitamin status and genetics with regard to the risk of SANS. Ultimately, understanding the mechanism(s) behind this will provide a means to predict, prevent, or treat these ophthalmologic pathologies in astronauts, and terrestrial populations.

S M Smith↗