Photorefractive Keratectomy and Laser-Assisted In Situ Keratomileusis on 6-Month Space Missions.

BACKGROUND: This article documents the stability of photorefractive keratectomy (PRK) and laser-assisted in situ keratomileusis (LASIK) in two astronauts during 6-mo missions to the International Space Station.CASE REPORTS: Ocular examinations including visual acuity, cycloplegic refraction, slit lamp examination, corneal topography, central corneal thickness, optical biometry (axial length/keratometry), applanation tonometry, and dilated fundus examination were performed on each astronaut before and after their missions, and in-flight visual acuity testing was done on flight day 30, 90, and R-30 (30 d before return). They were also questioned regarding visual changes during flight.DISCUSSION: We documented stable vision in both PRK and LASIK astronauts during liftoff, entry into microgravity, 6 mo on the International Space Station, descent, and landing. Our results suggest that both PRK and LASIK are stable and well tolerated during long-duration spaceflight.Gibson CR, Mader TH, Lipsky W, Schallhorn SC, Tarver WJ, Suresh R, Hauge TN, Brunstetter TJ. Photorefractive keratectomy and laser-assisted in situ keratomileusis on 6-month space missions. Aerosp Med Hum Perform. 2024; 95(5):278-281.

Evaluation of Optic Disc Edema in Long-Duration Spaceflight Crewmembers Using Retinal Photography.

BACKGROUND: Long-duration spaceflight crewmembers are at risk for spaceflight-associated neuro-ocular syndrome (SANS). One of the earliest manifestations of SANS is optic disc edema (ODE), which could be missed using the subjective Frisén scale. The primary objective of this study is to determine the inter-rater and intrarater reliability of Frisén grade for SANS-induced ODE among a trained observer cohort. The secondary objective is to propose a standardized evaluation process for SANS-induced ODE across International Space Station Partner Agencies. METHODS: Retrospective, double-blinded diagnostic study. Preflight and postflight fundus photographs were presented to subject matter experts who identified and graded ODE. Pairs of images were also compared side-by-side for disc ranking. Grader concordance was assessed for Frisén grading and disc ranking. RESULTS: Expert graders identified Grade 1 ODE in 17.35% of images from 62 crewmembers (9 female, mean [SD] age, 47.81 [5.19] years). Grades 2 and 3 were identified less than 2% of the time. Concordance in Frisén grades among pairs of graders was 70.99%. Graders identified a difference in preflight and postflight fundus photographs 17.21% of the time when using disc ranking. Pairs of graders had complete concordance in disc ranking 79.79% of the time. Perfect intrarater agreement between Frisén grade and disc ranking occurred 77.7% of the time. CONCLUSIONS: These findings demonstrate intergrader and intragrader variability when using the Frisén scale to identify SANS-induced ODE, which is typically milder in presentation than terrestrial cases of idiopathic intracranial hypertension. It is possible to miss early ODE on fundoscopy alone, making it insufficient as a sole criterion for the diagnosis of SANS. A more sensitive and objective method of surveillance is necessary to monitor international crewmembers for ODE, perhaps using a multimodal approach that includes technology such as optical coherence tomography.

Incidence and Progression of Chorioretinal Folds During Long-Duration Spaceflight.

Importance: The primary contributing factor for development of chorioretinal folds during spaceflight is unknown. Characterizing fold types that develop and tracking their progression may provide insight into the pathophysiology of spaceflight-associated neuro-ocular syndrome and elucidate the risk of fold progression for future exploration-class missions exceeding 12 months in duration. Objective: To determine the incidence and presentation of chorioretinal folds in long-duration International Space Station crew members and objectively quantify the progression of choroidal folds during spaceflight. Design, Setting, and Participants: In this retrospective cohort study, optical coherence tomography scans of the optic nerve head and macula of crew members completing long-duration spaceflight missions were obtained on Earth prior to spaceflight and during flight. A panel of experts examined the scans for the qualitative presence of chorioretinal folds. Peripapillary total retinal thickness was calculated to identify eyes with optic disc edema, and choroidal folds were quantified based on surface roughness within macular and peripapillary regions of interest. Interventions or Exposures: Spaceflight missions ranging 6 to 12 months. Main Outcomes and Measures: Incidence of peripapillary wrinkles, retinal folds, and choroidal folds; peripapillary total retinal thickness; and Bruch membrane surface roughness. Results: A total of 36 crew members were analyzed (mean [SD] age, 46 [6] years; 7 [19%] female). Chorioretinal folds were observed in 12 of 72 eyes (17%; 6 crew members). In eyes with early signs of disc edema, 10 of 42 (24%) had choroidal folds, 4 of 42 (10%) had inner retinal folds, and 2 of 42 (5%) had peripapillary wrinkles. Choroidal folds were observed in all eyes with retinal folds and peripapillary wrinkles. Macular choroidal folds developed in 7 of 12 eyes (4 of 6 crew members) with folds and progressed with mission duration; these folds extended into the fovea in 6 eyes. Circumpapillary choroidal folds developed predominantly superior, nasal, and inferior to the optic nerve head and increased in prevalence and severity with mission duration. Conclusions and Relevance: Choroidal folds were the most common fold type to develop during spaceflight; this differs from reports in idiopathic intracranial hypertension, suggesting differences in the mechanisms underlying fold formation. Quantitative measures demonstrate the development and progression of choroidal folds during weightlessness, and these metrics may help to assess the efficacy of spaceflight-associated neuro-ocular syndrome countermeasures.

Persistent Globe Flattening in Astronauts following Long-Duration Spaceflight.

Posterior globe flattening has been well-documented in astronauts both during and after long-duration space flight (LDSF) and has been observed as early as 10 days into a mission on the International Space Station. Globe flattening (GF) is thought to be caused by the disc centred anterior forces created by elevated volume and/or pressure within the optic nerve sheath (ONS). This might be the result of increased intracranial pressure, increased intraorbital ONS pressure from compartmentalisation or a combination of these mechanisms. We report posterior GF in three astronauts that has persisted for 7 years or more following their return from LDSFs suggesting that permanent scleral remodelling may have occurred.

Red risks for a journey to the red planet: The highest priority human health risks for a mission to Mars.

NASA's plans for space exploration include a return to the Moon to stay-boots back on the lunar surface with an orbital outpost. This station will be a launch point for voyages to destinations further away in our solar system, including journeys to the red planet Mars. To ensure success of these missions, health and performance risks associated with the unique hazards of spaceflight must be adequately controlled. These hazards-space radiation, altered gravity fields, isolation and confinement, closed environments, and distance from Earth-are linked with over 30 human health risks as documented by NASA's Human Research Program. The programmatic goal is to develop the tools and technologies to adequately mitigate, control, or accept these risks. The risks ranked as "red" have the highest priority based on both the likelihood of occurrence and the severity of their impact on human health, performance in mission, and long-term quality of life. These include: (1) space radiation health effects of cancer, cardiovascular disease, and cognitive decrements (2) Spaceflight-Associated Neuro-ocular Syndrome (3) behavioral health and performance decrements, and (4) inadequate food and nutrition. Evaluation of the hazards and risks in terms of the space exposome-the total sum of spaceflight and lifetime exposures and how they relate to genetics and determine the whole-body outcome-will provide a comprehensive picture of risk profiles for individual astronauts. In this review, we provide a primer on these "red" risks for the research community. The aim is to inform the development of studies and projects with high potential for generating both new knowledge and technologies to assist with mitigating multisystem risks to crew health during exploratory missions.

Optic Nerve Tortuosity on Earth and in Space.

INTRODUCTION: Spaceflight Associated Neuro-ocular Syndrome (SANS) results from long-duration spaceflight and presents with a constellation of signs (e.g., optic disc edema, choroidal folds, globe flattening, refractive error shifts, etc.). Optic nerve tortuosity (ONT) has been detected in approximately 47% of astronauts after long-duration spaceflight but has not yet been fully analyzed. This review examines terrestrial ONT in order to better understand how the condition is caused and measured.METHODS: References were identified by PubMed and ScienceDirect searches covering 1955 to October 2018 using the terms "optic nerve tortuosity," "optic nerve kinking," "optic disc torsion," "optic kinking," and "ocular torsion." Additional references were identified by searching relevant articles.RESULTS: ONT measurements have evolved and become more objective. One measure consists of meeting two criteria: 1) lack of optic nerve congruity in >1 coronal section; and 2) subarachnoid space dilation. This "criteria measure" is objective, sensitive, and specific for determining the presence of tortuosity. Another measure is the tortuosity index, which offers additional benefits by measuring the degree of ONT, including the potential to track changes over time. There are numerous terrestrial ONT causes, including intracranial hypertension, hydrocephalus, Chiari malformation, neurofibromatosis, glaucoma, and progeria, among others.DISCUSSION: To accurately measure ONT, it is crucial to adhere to objective, standardized techniques. The tortuosity index offers the potential to measure intraindividual change in ONT. Among the varied conditions associated with ONT, one commonality is pressure change. The impact of intracranial pressure on the vascular system and vice versa may offer insight into what is occurring in space.Scott RA, Tarver WJ, Brunstetter TJ, Urquieta E. Optic nerve tortuosity on Earth and in space. Aerosp Med Hum Perform. 2020; 91(2):91-97.

Origins of Cerebral Edema: Implications for Spaceflight-Associated Neuro-Ocular Syndrome.

BACKGROUND: Spaceflight-associated neuro-ocular syndrome (SANS) was first described in 2011 and is associated with structural ocular changes found to occur in astronauts after long-duration missions. Despite multiple insufficient potential terrestrial models, an understanding of the etiology has yet to be described. EVIDENCE ACQUISITION: A systematic review was conducted on literature published about the pathophysiology of cerebral edema. Databases searched include PubMed, Scopus, and the Texas Medical Center Online Library. This information was then applied to create theories on mechanisms on SANS etiology. RESULTS: Cerebral edema occurs through 2 general mechanisms: redistribution of ions and water intracellularly and displacement of ions and water from the vascular compartment to the brain parenchyma. These processes occur through interconnected endocrine and inflammatory pathways and involve mediators such as cytokines, matrix metalloproteases, nitric oxide, and free radicals. The pathways ultimately lead to a violation of cellular membrane ionic gradients and blood-brain barrier degradation. By applying the principles of cerebral edema pathophysiology to the optic disc edema (ODE) see in SANS, several theories regarding its etiology can be formed. Venous stasis may lead to ODE through venous and capillary distension and leak, as well as relative hypoxia and insufficient ATP substrate delivery causing axoplasmic flow stasis and local oxidative stress. CONCLUSIONS: Using the pathophysiology of cerebral edema as a model, hypotheses can be inferred as to the etiology of ODE in SANS. Further studies are needed to determine the presence and contribution of local vascular stasis and resulting inflammation and oxidative stress to the pathophysiology of SANS.

Space flight-associated neuro-ocular syndrome (SANS).

Interesting novel and somewhat perplexing physiologic and pathologic neuro-ocular findings have been documented in astronauts during and after long duration space flight (LDSF). These findings collectively have been termed the "space flight-associated neuro-ocular syndrome" (SANS). The National Aeronautics and Space Administration (NASA) in the United States has meticulously and prospectively documented the clinical, ultrasound, optical coherence tomography imaging, and radiographic findings of SANS including unilateral and bilateral optic disc edema, globe flattening, choroidal and retinal folds, hyperopic refractive error shifts, and nerve fiber layer infarcts (i.e., cotton wool spots). NASA and collaborating researchers continue to study SANS in preparation for future manned missions to space, including continued trips to the ISS, a return to the moon, or perhaps new voyages to the asteroid belt, or the planet, Mars.

Evaluation of single pixel step sizes in visual acuity assessment.

PURPOSE: Adaptive thresholding procedures (e.g., ZEST) benefit from testing near the current estimate of threshold. Therefore, small increments may improve precision of these techniques. We evaluated the validity of visual acuity assessment when letters are not constrained to a multiple of 5 pixels high. METHODS: Snellen letters were presented over a ±5 pixel range spanning the final threshold estimate. Sizes that were a multiple of 5 pixels (e.g., 20 and 25) were presented 160 times, and other sizes were presented 40 times. This resulted in 320 letter presentations at multiples of 5 and at non-multiples of 5. Post hoc ZEST procedures were used to compute acuity threshold estimates based on testing at those two sets of sizes. Two subjects participated: subject 1 for the right and left eyes and subject 2 in two sessions with binocular viewing. Psychometric functions were fit to the data and were used to model simulated observers. Simulations were run for each data set, and the number of presentations at each size matched the number presented to the subject. Ninety percent limits for proportion correct at each letter size were determined from the simulation data, and these limits were used as criteria for identifying outliers in the subject's data. RESULTS: No significant difference in acuity thresholds were found when letters were rendered in multiples of 5 pixel heights vs. letters without this constraint. Empirical data fell within the bounds defined by simulations, with no idiosyncratic results found for either set of letter sizes. CONCLUSIONS: Letter sizes that do not conform to a multiple of 5 pixel letter height yield valid acuity scores. This facilitates adaptive psychometric procedures for acuity testing, such as ZEST and QUEST, in which letter sizes are selected to be as close to the current estimate of threshold size as possible.

Why preoperative acuity predicts postoperative acuity in wavefront-guided LASIK.

PURPOSE: To critically evaluate the following clinical wisdom regarding custom (wavefront-guided) laser in situ keratomileusis (LASIK) that subjects with better-than-average best-corrected visual acuity (BCVA) before surgery have a greater risk of losing BCVA postoperatively than do subjects with worse-than-average BCVA before surgery. METHODS: High contrast BCVA was measured once before and 3 months after custom LASIK in one eye of 79 subjects. Preoperative spherical equivalent refractive error ranged between -1.00 and -10.38 D. The sample was divided into one of two subsamples: eyes that had better-than-average preoperative BCVA (<-0.11 logMAR) and eyes that had average or worse-than-average preoperative BCVA (≥-0.11 logMAR). Controls were implemented for retinal magnification and for the statistical phenomenon of regression to the mean of the preoperative acuity measurement. RESULTS: On average, for the entire sample, moving the correction from the spectacle plane to the corneal plane increased letter acuity 4.7% (1 letter, 0.02 logMAR). For each subsample, the percentage regression to the mean was 57.24%. After correcting for magnification effects and regression to the mean, eyes with better-than-average preoperative acuity had a small but significant gain in acuity (∼1 letter, p = 0.040) that was nearly identical to the gain for eyes with worse-than-average preoperative acuity (∼1.5 letters, p = 0.002). CONCLUSIONS: Custom LASIK produced a statistically significant gain in visual acuity after correction for magnification effects. Dividing the sample into two subsamples based on preoperative acuity confirmed the common clinical observation that eyes with better-than-average acuity tend to remain the same or lose acuity, whereas eyes with worse-than-average acuity tend to gain acuity. However, when only one acuity measurement is taken at a single time point and the sample is subsampled nonrandomly, this clinical observation is due to a statistical artifact (regression to the mean) and is not attributable to the surgery.

Controlled induction of spherical aberration with custom soft contact lenses.

BACKGROUND: This study investigated the non-invasive induction of spherical aberration (SA) levels consistent with complication-free wavefront-guided (WFG) refractive surgery using custom WFG soft contact lenses and quantified the resulting impact on visual performance. METHODS: Twelve healthy individuals of typical military age (mean of 26.08 +/- 1.92 years) meeting the inclusion criteria of emmetropia (less than +/- 0.50 DS and less than +/- 0.50 DC) as measured by subjective refraction served as subjects. Five plano lenses were manufactured to induce a range of SA typical of those encountered after refractive surgery. The measured SA values over a 6 mm artificial pupil in these five lenses were -0.224 microm, 0.074 microm, 0.214 microm, 0.495 microm and 0.621 microm. For each subject, the level of total ocular aberrations through 10 Zernike radial orders over a 6 mm pupil was measured with a custom Shack-Hartmann wavefront sensor, while wearing each lens. Visual performance was evaluated using high contrast visual acuity (HCVA) measured through a 6 mm artificial pupil. RESULTS: Custom WFG soft contact lenses can be manufactured to include the range of SA that occurs with complication-free refractive surgery (-0.20 microm to +0.60 microm) and produces a change in SA within a similar range when worn on the eye. High contrast visual performance with these lenses varied, depending on the amount of SA in each lens. Visual performance worsened with greater amounts of positive or negative SA and a quadratic fit to the data peaked at +0.209 microm. CONCLUSIONS: Defined levels of SA can be manufactured and induced (non-invasively) with WFG soft contact lenses and their effect on logMAR high contrast visual performance can be measured. Results show that subjects' best logMAR HCVA occurs with the presence of positive residual SA. When designing the actual test lens, the targeted change in aberrations for each subject will likely be better achieved by first measuring the aberrations of a template lens on the eye and then compensating for unique subject dependent eye-lens interactions.

Magnetic field coil measurements of the accuracy of extreme gaze ocular fixation.

PURPOSE: (1) To assess the adequacy of the magnetic field coil method (MFCM) for measures of extreme gaze ocular fixation; and (2) to measure the accuracy of ocular fixation for a short duration at gaze angles of 10 to 40 degrees. METHODS: Seven subjects participated. Two experiments were performed on the same day. In both experiments, the head and eye were rotated in opposite directions. In the first experiment, search coil slippage was assessed using photographs of a scleral search coil worn on one eye. These photographs were taken with a slitlamp biomicroscope equipped with a digital photography system as subjects rotated the eyes through nasal angles up to 40 degrees. In the second experiment, measures of ocular position were made using the MFCM as the eye was rotated through nasal angles up to 40 degrees to fixate a light-emitting diode target under two conditions. In one condition, subjects simply aimed the eye at the target. In the other, subjects placed a foveal afterimage on the target as the target was viewed through a pinhole. RESULTS: Temporal search coil slippage >10 arc min was noted for three subjects. For one subject, this slippage occurred at gaze angles > or =20 degrees, whereas for the other subjects, the slippage appeared at gaze angles of > or =30 degrees. Ocular fixation had to be assessed from the differences in fixation position between the two conditions in the second experiment because of search coil slippage and because the relationship between the anterior and posterior portions of the eyes changed for some individuals as the gaze angle changed. Fixation was usually accurate (within 10 arc min). There were occasional instances where fixation errors >15 arc min occurred, but we believe that all but one of these cases were attributable to poor localization of the afterimage. CONCLUSION.: Scleral search coils can slip on some individuals in extreme gaze. Search coils may also be inadequate to indicate the direction of the fovea in extreme gaze for some individuals because the relationship between the anterior and posterior portions can change with gaze angle. Once artifacts associated with the MFCM and localization of the afterimage are accounted for, ocular fixation is almost always within 10 arc min of the fixation target at gaze angles of 10 to 40 degrees.