Peripheral Choroidal Response to Localized Defocus Blur: Influence of Native Peripheral Aberrations.

Purpose: This study aims to examine the short-term peripheral choroidal thickness (PChT) response to signed defocus blur, both with and without native peripheral aberrations. This examination will provide insights into the role of peripheral aberration in detecting signs of defocus. Methods: The peripheral retina (temporal 15°) of the right eye was exposed to a localized video stimulus in 11 young adults. An adaptive optics system induced 2D myopic or hyperopic defocus onto the stimulus, with or without correcting native peripheral ocular aberrations (adaptive optics [AO] or NoAO defocus conditions). Choroidal scans were captured using Heidelberg Spectralis OCT at baseline, exposure (10, 20, and 30 minutes), and recovery phases (4, 8, and 15 minutes). Neural network-based automated MATLAB segmentation program measured PChT changes from OCT scans, and statistical analysis evaluated the effects of different optical conditions over time. Results: During the exposure phase, NoAO myopic and hyperopic defocus conditions exhibited distinct bidirectional PChT alterations, showing average thickening (10.0 ± 5.3 µm) and thinning (-9.1 ± 5.5 µm), respectively. In contrast, induced AO defocus conditions did not demonstrate a significant change from baseline. PChT recovery to baseline occurred for all conditions. The unexposed fovea did not show any significant ChT change, indicating a localized ChT response to retinal blur. Conclusions: We discovered that the PChT response serves as a marker for detecting peripheral retinal myopic and hyperopic defocus blur, especially in the presence of peripheral aberrations. These findings highlight the significant role of peripheral oriented blur in cueing peripheral defocus sign detection.

Short-Term Myopic Defocus and Choroidal Thickness in Children and Adults.

Purpose: Studies report conflicting findings regarding choroidal thickness changes in response to myopic defocus in humans. This study aimed to investigate the choroidal response to myopic defocus in children and adults using automated analysis. Methods: Participants (N = 46) were distance-corrected in both eyes and viewed a movie on a screen for 10 minutes. Two optical coherence tomography (OCT) radial scans were collected for each eye, then +3 diopters was added to one eye. Participants continued to watch the movie, OCT scans were repeated every 10 minutes for 50 minutes, and then recovery was assessed at 60 and 70 minutes. Defocus was interrupted for approximately two out of each 10 minutes for OCT imaging. OCT images were analyzed using an automated algorithm and trained neural network implemented in MATLAB to determine choroidal thickness at each time point. Repeated-measures ANOVA was used to assess changes with time in three age groups (6-17, 18-30, and 31-45 years) and by refractive error group (myopic and nonmyopic). Results: Choroidal thickness was significantly associated with spherical equivalent refraction, with the myopic group having a thinner choroid than the nonmyopic group (P < 0.001). With imposed myopic defocus, there were no significant changes in choroidal thickness at any time point for any age group and for either refractive error group (P > 0.05 for all). Conclusions: Findings demonstrate that, using the described protocol, the choroidal thickness of children and adults does not significantly change in response to short-term, full-field myopic defocus, in contrast to several previously published studies.

Human deprivation amblyopia: treatment insights from animal models.

Amblyopia is a common visual impairment that develops during the early years of postnatal life. It emerges as a sequela to eye misalignment, an imbalanced refractive state, or obstruction to form vision. All of these conditions prevent normal vision and derail the typical development of neural connections within the visual system. Among the subtypes of amblyopia, the most debilitating and recalcitrant to treatment is deprivation amblyopia. Nevertheless, human studies focused on advancing the standard of care for amblyopia have largely avoided recruitment of patients with this rare but severe impairment subtype. In this review, we delineate characteristics of deprivation amblyopia and underscore the critical need for new and more effective therapy. Animal models offer a unique opportunity to address this unmet need by enabling the development of unconventional and potent amblyopia therapies that cannot be pioneered in humans. Insights derived from studies using animal models are discussed as potential therapeutic innovations for the remediation of deprivation amblyopia. Retinal inactivation is highlighted as an emerging therapy that exhibits efficacy against the effects of monocular deprivation at ages when conventional therapy is ineffective, and recovery occurs without apparent detriment to the treated eye.

Effects of head-down tilt on optic nerve sheath diameter in healthy subjects.

PURPOSE: Intracranial pressure increases in head-down tilt (HDT) body posture. This study evaluated the effect of HDT on the optic nerve sheath diameter (ONSD) in normal subjects. METHODS: Twenty six healthy adults (age 28 [4.7] years) participated in seated and 6° HDT visits. For each visit, subjects presented at 11:00 h for baseline seated scans and then maintained a seated or 6° HDT posture from 12:00 to 15:00 h. Three horizontal axial and three vertical axial scans were obtained at 11:00, 12:00 and 15:00 h with a 10 MHz ultrasonography probe on the same eye, randomly chosen per subject. At each time point, horizontal and vertical ONSD (mm) were quantified by averaging three measures taken 3 mm behind the globe. RESULTS: In the seated visit, ONSDs were similar across time (p > 0.05), with an overall mean (standard deviation) of 4.71 (0.48) horizontally and 5.08 (0.44) vertically. ONSD was larger vertically than horizontally at each time point (p < 0.001). In the HDT visit, ONSD was significantly enlarged from baseline at 12:00 and 15:00 h (p < 0.001 horizontal and p < 0.05 vertical). Mean (standard error) horizontal ONSD change from baseline was 0.37 (0.07) HDT versus 0.10 (0.05) seated at 12:00 h (p = 0.002) and 0.41 (0.09) HDT versus 0.12 (0.06) seated at 15:00 h (p = 0.002); mean vertical ONSD change was 0.14 (0.07) HDT versus -0.07 (0.04) seated at 12:00 h (p = 0.02) and 0.19 (0.06) HDT versus -0.03 (0.04) seated at 15:00 h (p = 0.01). ONSD change in HDT was similar between 12:00 and 15:00 h (p ≥ 0.30). Changes at 12:00 h correlated with those at 15:00 h for horizontal (r = 0.78, p < 0.001) and vertical ONSD (r = 0.73, p < 0.001). CONCLUSION: The ONSD increased when body posture transitioned from seated to HDT position without any further change at the end of the 3 h in HDT.

Neuroretinal Rim Response to Transient Intraocular Pressure Challenge Predicts the Extent of Retinal Ganglion Cell Loss in Experimental Glaucoma.

Purpose: To determine if the optic nerve head (ONH) response to transient elevated intraocular pressure (IOP) can predict the extent of neural loss in the nonhuman primate experimental glaucoma model. Methods: The anterior chamber pressure of 21 healthy animals (5.4 ± 1.2 years, 8 female) was adjusted to 25 mm Hg for two hours followed by 10 mm Hg for an additional two hours. For the duration of IOP challenge the ONH was imaged using radial optical coherence tomography (OCT) scans at five-minute intervals. Afterward, a randomized sample of 14 of these subjects had unilateral experimental glaucoma induced and were monitored with OCT imaging, tonometry, and ocular biometry at two-week intervals. Results: With pressure challenge, the maximum decrease in ONH minimum rim width (MRW) was 40 ± 10.5 µm at 25 mm Hg and was correlated with the precannulation MRW, Bruch's membrane opening (BMO) position, and the anterior lamina cribrosa surface position (P = 0.01). The maximum return of MRW at 10 mm Hg was 16.1 ± 5.0 µm and was not associated with any precannulation ONH feature (P = 0.24). However, healthy eyes with greater thickness return at 10 mm Hg had greater loss of MRW and retinal nerve fiber layer (RNFL) at a cumulative IOP of 1000 mm Hg · days after induction of experimental glaucoma. In addition, MRW and RNFL thinning was correlated with an increase in axial length (P < 0.01). Conclusion: This study's findings suggest that the ONH's response to transient changes in IOP are associated with features of the ONH and surrounding tissues. The neural rim properties at baseline and the extent of axial elongation are associated with the severity of glaucomatous loss in the nonhuman primate model.

Correlates of Outdoor Time in Schoolchildren From Families Speaking Nonofficial Languages at Home: A Multisite Canadian Study.

BACKGROUND: Previous research shows that children from ethnic minority groups spend less time outdoors. Using data collected in 3 regions of Canada, we investigated the correlates of outdoor time among schoolchildren who spoke a nonofficial language at home. METHODS: A total of 1699 children were recruited from 37 schools stratified by area-level socioeconomic status and type of urbanization. Among these, 478 spoke a nonofficial language at home. Children's outdoor time and data on potential correlates were collected via questionnaires. Gender-stratified linear multiple regression models examined the correlates of outdoor time while controlling for age and sampling variables. RESULTS: In boys, higher independent mobility, higher outdoor air temperature, mobile phone ownership, having older parents, and parents who biked to work were associated with more outdoor time. Boys living in suburban (vs urban) areas spent less time outdoors. The association between independent mobility and outdoor time became weaker with increasing age for boys. In girls, lower parental education and greater parental concerns about neighborhood safety and social cohesion were associated with less outdoor time. CONCLUSIONS: Correlates of outdoor time differ by gender and span the social ecological model underscoring the need for gender-sensitized interventions targeted at individual, family, social, and physical environmental correlates to increase outdoor time.

Identification of Factors Associated With the Development of Optic Disc Edema During Spaceflight.

Importance: Approximately 70% of crew members who complete long-duration missions to the International Space Station develop signs of optic disc edema, a hallmark finding of spaceflight-associated neuro-ocular syndrome. The onset and magnitude of edema differ across individuals, and the reason for this variability remains unknown. Identifying risk factors for spaceflight-induced disc edema is important because this condition may become more severe during extended-duration missions to the moon and Mars and could be associated with irreversible vision loss. Objective: To assess whether preflight indicators of crowded optic nerve head morphology, other ocular measures (such as choroid thickness and axial length), body weight, body mass index, sex, age, and previous flight experience are associated with optic disc edema development. Design, Setting, and Participants: This cohort study analyzed ocular, body weight, and demographic data collected from 31 US and international crew members before, during, and after spaceflight at the NASA Johnson Space Center and International Space Station. Ocular factors assessed included preflight and in-flight peripapillary total retinal thickness, minimum rim width, optic cup volume, mean cup depth, mean cup width, cup-disc ratio, Bruch membrane opening area, retinal nerve fiber layer thickness, choroid thickness, axial length, and refractive error. In addition, body weight, body mass index, sex, age, and previous spaceflight experience were assessed for associations with optic disc edema development. The data were analyzed from August 2021 to June 2022. Exposure: Approximately 6 to 12 months of spaceflight. Main Outcomes and Measures: In-flight increases in peripapillary total retinal thickness. Linear mixed models were used to assess for associations between a wide range of risk factors and in-flight increases in peripapillary total retinal thickness, which is a sensitive objective measure for detecting optic disc edema. Results: This study included 31 International Space Station crew members with a mean (SD) age of 46.9 (6.0) years (25 men [80.6%]). During spaceflight, mean (SE) peripapillary total retinal thickness increased from 392.0 (5.8) µm to 430.2 (9.6) µm (P < .001), and greater individual changes were associated with smaller preflight cup volume (slope [SE], -62.8 [18.9]; P = .002), shallower preflight cup depth (slope [SE], -0.11 [0.03]; P < .001), and narrower preflight cup width (slope [SE], -0.03 [0.01]; P = .03). No associations were observed between changes in peripapillary total retinal thickness and any other variable evaluated. Conclusions and Relevance: Findings of this cohort study suggest that smaller optic cup morphology may be associated with optic disc edema development during spaceflight. Crew members with this cup profile may benefit from enhanced ophthalmic monitoring during spaceflight and use of countermeasures against spaceflight-associated neuro-ocular syndrome.

Electroretinographic responses to luminance and cone-isolating white noise stimuli in macaques.

Electroretinograms (ERGs) are mass potentials with a retinal origin that can be measured non-invasively. They can provide information about the physiology of the retina. Often, ERGs are measured to flashes that are highly unnatural stimuli. To obtain more information about the physiology of the retina, we measured ERGs with temporal white noise (TWN) stimuli that are more natural and keep the retina in a normal range of operation. The stimuli can be combined with the silent substitution stimulation technique with which the responses of single photoreceptor types can be isolated. We characterized electroretinogram (ERG) responses driven by luminance activity or by the L- or the M-cones. The ERGs were measured from five anesthetized macaques (two females) to luminance, to L-cone isolating and to M-cone isolating stimuli in which luminance or cone excitation were modulated with a TWN profile. The responses from different recordings were correlated with each other to study reproducibility and inter-individual variability. Impulse response functions (IRFs) were derived by cross-correlating the response with the stimulus. Modulation transfer functions (MTFs) were the IRFs in the frequency domain. The responses to luminance and L-cone isolating stimuli showed the largest reproducibility. The M-cone driven responses showed the smallest inter-individual variability. The IRFs and MTFs showed early (high frequency) components that were dominated by L-cone driven signals. A late component was equally driven by L- and M-cone activity. The IRFs showed characteristic similarities and differences relative to flash ERGs. The responses to TWN stimuli can be used to characterize the involvement of retinal cells and pathways to the ERG response. It can also be used to identify linear and non-linear processes.

Longitudinal In Vivo Changes in Radial Peripapillary Capillaries and Optic Nerve Head Structure in Non-Human Primates With Early Experimental Glaucoma.

Purpose: There is conflicting evidence regarding whether a loss of radial peripapillary capillaries (RPCs) precedes neuronal loss in glaucoma. We examined the time course of in vivo changes in RPCs, optic nerve head (ONH) structure, and retinal nerve fiber layer thickness (RNFLT) in experimental glaucoma (EG). Methods: Spectral domain optical coherence tomography images were acquired before and approximately every two weeks after inducing unilateral EG in nine rhesus monkeys to quantify mean anterior lamina cribrosa surface depth (ALCSD), minimum rim width (MRW), and RNFLT. Perfused RPC density was measured from adaptive optics scanning laser ophthalmoscope images acquired on the temporal half of the ONH. The time of first significant change was quantified as when values fell and remained outside of the 95% confidence interval established from control eyes. Results: Mean ALCSD and/or MRW were the first parameters to change in eight EG eyes. RPC density changed first in the ninth. At their first points of change, mean ALCSD posteriorly deformed by 100.2 ± 101.2 µm, MRW thinned by 82.3 ± 65.9 µm, RNFLT decreased by 25 ± 14 µm, and RPC density decreased by 4.5 ± 2.1%. RPC density decreased before RNFL thinning in 5 EG eyes. RNFLT decreased before RPC density decreased in two EG eyes, whereas two EG eyes had simultaneous changes. Conclusions: In most EG eyes, RPC density decreased before (or simultaneous with) a change in RNFLT, suggesting that vascular factors may play a role in axonal loss in some eyes in early glaucoma.

Patients Achieving 90°/45°/0° Intraoperative Stability Do Not Require Hip Precautions Following Posterior Approach Total Hip Arthroplasty: A Prospective Randomized Study.

BACKGROUND: Hip precautions are traditionally employed after posterior total hip arthroplasty (THA). The primary purpose was to investigate the necessity of hip precautions after posterior approach THA. We hypothesized that eliminating precautions in patients that achieved appropriate intraoperative stability would not increase the dislocation rate. METHODS: Randomized controlled trial of 346 consecutive eligible patients undergoing primary THA with a mean follow-up of 2.3 years (range 11 months to 3.7 years). EXCLUSION CRITERIA: lumbar fusion, scoliosis, abductor insufficiency, inability to achieve intraoperative stability with combined 90° flexion and 45° internal rotation in 0° adduction. Fisher's exact test was used to compare dislocation rates between the hip precaution (HP) control group and no hip precaution (NP) study group. In addition, Mann-Whitney U test was used to compare differences in HOOS JR scores at 2, 6, 12 weeks between groups. RESULTS: The dislocation rate was not increased in the NP (0/172: 0%) group compared to the HP group 4/174 (2.29%) (P = .418). All dislocations occurred in the precautions group, two of which required revision. There were no differences in mean HOOS Jr. scores at any 2, 6, or 12 weeks (P > .05 at all timepoints) (secondary outcome). CONCLUSION: Eliminating hip precautions in patients undergoing posterior approach THA that achieve 90°/45°/0° intraoperative stability does not increase the rate of dislocation. In fact, every dislocation occurred in patients receiving hip precautions. Short-term patient-reported outcome measures were not affected by hip precautions. Surgeons may discontinue the use of hip precautions as the standard of care in patients achieving 90°/45°/0° stability.

Comparison of macaque and human L- and M-cone driven electroretinograms.

PURPOSE: The macaque retina is often used as a model for the human retina. However, there are only a handful of direct in vivo comparisons of the retinal physiology in humans and macaques. In the current study, ERG responses to luminance, L-cone isolating and M-cone isolating stimuli with sinusoidal, sawtooth and square wave temporal profiles were measured. The results were compared with those obtained from human observers. METHODS: The responses from five anesthetized adult macaques were measured. Full field stimuli were created. L- and M-cone isolating stimuli were based on the triple silent substitution technique. Sinusoidal stimuli had temporal frequencies between 4 and 56 Hz in 4 Hz steps. Sawtooth stimuli with rapid-on ramp-off and with rapid-off ramp-on excitation profiles had a frequency of 4 Hz. Square stimuli were presented at 2 Hz. RESULTS: Macaque and human ERGs in response to L- and M-cone isolating stimuli reflect L/M opponency and luminance activity. In responses to sine waves, cone opponency dominates at low temporal frequencies (4-12 Hz); luminance dominates at high temporal frequencies. The responses to sawtooth and square wave stimuli reflect a mixture of chromatic and luminance activity. L:M response ratios vary between individuals both in macaques and humans. Macaques show more complex responses, including greater second harmonic contributions than those in humans. CONCLUSIONS: Macaque and human ERGs share basic underlying mechanisms reflecting L/M opponency and luminance activity. There may be quantitative differences possibly reflecting differences in contributions of inner retinal mechanisms to the ERGs.

Retinal ganglion cell ablation in guinea pigs.

Guinea pigs are a common model of human ocular conditions; however, their visual function has not been fully characterized. The purpose of this study was to determine the contributions of retinal ganglion cells to structural and functional measures in guinea pigs. Healthy adult guinea pigs (n = 12) underwent unilateral optic nerve crush. Retinal structure was assessed with spectral domain optical coherence tomography (OCT), and thickness of the ganglion cell/nerve fiber layer (GC/NFL) was determined. Visual function was assessed with optomotor tracking of a drifting grating and light adapted electroretinograms (ERGs). From flash ERGs, a-wave, b-wave, oscillatory potentials (OPs), and photopic negative response (PhNR) were analyzed. From pattern ERGs, N1P1 and P1N2 were analyzed. Histological studies were done at various time points for ganglion cell quantification. Optomotor tracking was absent in optic nerve crush eyes following optic nerve crush. Significant thinning of the GC/NFL was evident four weeks following the crush. Flash ERGs revealed a significant reduction in the OP1 amplitude two weeks following crush (P < 0.01) and in the PhNR amplitude six weeks following crush (P < 0.01). There were no significant changes in a-wave, b-wave, or pattern ERG responses (P > 0.05 for all). In vivo OCT imaging showed progressive thinning of inner retinal layers. Ganglion cell density, quantified histologically, was significantly reduced by 75% in the optic nerve crush eye compared to the control eye at four weeks following crush. These findings indicate that retinal ganglion cells contribute to the PhNR and OP1 components of the full field flash ERG, but not significantly to the pattern ERG in guinea pigs. This study demonstrates that OCT imaging and full field flash ERGs are valuable in assessing retinal ganglion cell loss in vivo in guinea pigs and will help to further establish the guinea pig as a model of human ocular pathologies.

Optic Nerve Head Morphological Changes Over 12 Hours in Seated and Head-Down Tilt Postures.

Purpose: The purpose of this study was to determine changes in optic nerve head (ONH) morphology in seated and 6° head-down tilt (HDT) postures over a 12-hour period. Methods: Thirty eyes of 30 healthy human subjects (15 females) were included. Composite radial and circular optical coherence tomography (OCT) scans centered on the ONH, intraocular pressure (IOP), and optic nerve sheath diameter (ONSD) were acquired every two hours from 7 a.m. to 7 p.m. for both seated (n = 30) and HDT (n = 10) sessions. Global minimum rim width (BMO-MRW), total retinal thickness (TRT), retinal nerve fiber layer thickness (RNFLT), and Bruch's membrane opening (BMO) height were quantified. Results: BMO-MRW decreased an average of 9.55 ± 8.03 µm (P < 0.01) over 12 hours in a seated position (range, -26.64 to +3.36 µm), and thinning was greater in females (-13.56 vs. -5.55 µm, P = 0.004). Modest decreases in TRT from the BMO to 500 µm (P < 0.04) and RNFLT for the 2.7, 3.5, and 4.2 mm circular scans (P < 0.02) were also observed. BMO-MRW thinning was not related to changes in IOP or ONSD (P = 0.34). In HDT, IOP and ONSD increased, BMO height moved anteriorly, and BMO-MRW thinning did not occur (P > 0.1). Conclusions: The neuroretinal rim thins throughout the day in healthy individuals, and this change cannot be explained by changes in IOP or ONSD during the same time period. A HDT posture blunts the neuroretinal rim thinning observed in a seated position, suggesting a role of the translaminar pressure difference.

Automatic Segmentation of Retinal Capillaries in Adaptive Optics Scanning Laser Ophthalmoscope Perfusion Images Using a Convolutional Neural Network.

Purpose: Adaptive optics scanning laser ophthalmoscope (AOSLO) capillary perfusion images can possess large variations in contrast, intensity, and background signal, thereby limiting the use of global or adaptive thresholding techniques for automatic segmentation. We sought to develop an automated approach to segment perfused capillaries in AOSLO images. Methods: 12,979 image patches were extracted from manually segmented AOSLO montages from 14 eyes and used to train a convolutional neural network (CNN) that classified pixels as capillaries, large vessels, background, or image canvas. 1764 patches were extracted from AOSLO montages of four separate subjects, and were segmented manually by two raters (ground truth) and automatically by the CNN, an Otsu's approach, and a Frangi approach. A modified Dice coefficient was created to account for slight spatial differences between the same manually and CNN-segmented capillaries. Results: CNN capillary segmentation had an accuracy (0.94), a Dice coefficient (0.67), and a modified Dice coefficient (0.90) that were significantly higher than other automated approaches (P < 0.05). There were no significant differences in capillary density and mean segment length between manual ground-truth and CNN segmentations (P > 0.05). Conclusions: Close agreement between the CNN and manual segmentations enables robust and objective quantification of perfused capillary metrics. The developed CNN is time and computationally efficient, and distinguishes capillaries from areas containing diffuse background signal and larger underlying vessels. Translational Relevance: This automatic segmentation algorithm greatly increases the efficiency of quantifying AOSLO capillary perfusion images.

In vivo assessment of foveal geometry and cone photoreceptor density and spacing in children.

The fovea undergoes significant developmental changes from birth into adolescence. However, there is limited data examining cone photoreceptor density, foveal pit shape, and foveal avascular zone (FAZ) size in children. The purpose of this study was to determine whether overall foveal structure differs as a function of age and refractive status in children. Forty-eight healthy children (ages 5.8 to 15.8 years) underwent optical coherence tomography imaging to quantify foveal point thickness and foveal pit diameter, depth, and slope. Adaptive optics scanning laser ophthalmoscope (AOSLO) images of foveal capillaries and cone photoreceptors were acquired in a subset of children to quantify FAZ metrics and cone densities at 0.2, 0.3, and 0.5 mm eccentricities. Results show that foveal pit and FAZ metrics were not related to age, axial length, or refractive status. However, linear cone density was lower in myopic versus non-myopic children at eccentricities of 0.2 mm (mean ± SD = 50,022 ± 5,878 cones/mm2 vs 58,989 ± 4,822 cones/mm2, P < 0.001) and 0.3 mm (43,944 ± 5,547 cones/mm2 vs 48,622 ± 3,538 cones/mm2, P < 0.001). These results suggest FAZ and foveal pit metrics do not systematically differ with age in children, while myopic eyes have decreased linear cone density near the foveal center. Significance Statement: The development of the fovea begins prior to birth and continues through the early teenage years until it reaches adult-like properties. Although the majority of changes during childhood are related to the maturation and migration of cone photoreceptors, in vivo data describing cone packing in children is limited. We assessed overall foveal structure in children as young as 5.8 years old by quantifying cone density and spacing, foveal avascular zone size, and foveal pit morphometry to investigate potential structural differences as a function of age and refractive status. While foveal avascular zone and foveal pit metrics did not significantly differ with age, results indicate that myopic children have lower linear cone densities close to the foveal center compared to non-myopic children.

Association of Long-Duration Spaceflight With Anterior and Posterior Ocular Structure Changes in Astronauts and Their Recovery.

Importance: During long-duration spaceflights, nearly all astronauts exhibit some change in ocular structure within the spectrum of spaceflight-associated neuro-ocular syndrome. Objective: To quantitatively determine in a prospective study whether changes in ocular structures hypothesized to be associated with the development of spaceflight-associated neuro-ocular syndrome occur during 6-month missions on board the International Space Station (ISS). Design, Setting, and Participants: The Ocular Health ISS Study of astronauts is a longitudinal prospective cohort study that uses objective quantitative imaging modalities. The present cohort study investigated the ocular structure of 11 astronauts before, during, and after a 6-month mission on board the ISS. Main Outcomes and Measures: Changes in ocular structure (peripapillary edema, axial length, anterior chamber depth, and refraction) hypothesized to be associated with the development of spaceflight-associated neuro-ocular syndrome during 6-month missions on board the ISS were assessed. Statistical analyses were conducted from August 2018 to January 2019. Results: Before launch, the 11 astronauts were a mean (SD) age of 45 (5) years, a mean (SD) height of 1.76 (0.05) m, and a mean (SD) weight of 75.3 (7.1) kg. Six astronauts did not have prior spaceflight experience, 3 had completed short-duration missions on board the Space Shuttle, and 2 had previous long-duration spaceflight missions on board the ISS. Their mean (SD) duration on board the ISS in the present study was 170 (19) days. Optic nerve head rim tissue and peripapillary choroidal thickness increased from preflight values during early spaceflight, with maximal change typically near the end of the mission (mean change in optic nerve head rim tissue thickness on flight day 150: 35.7 µm; 95% CI, 28.5-42.9 µm; P < .001; mean choroidal thickness change on flight day 150: 43 µm; 95% CI, 35-46 µm; P < .001). The mean postflight axial length of the eye decreased by 0.08 mm (95% CI, 0.10-0.07 mm; P < .001) compared with preflight measures, and this change persisted through the last examination (1 year after spaceflight: 0.05 mm; 95% CI, 0.07-0.03 mm; P < .001). Conclusions and Relevance: This study found that spaceflight-associated peripapillary optic disc edema and choroid thickening were observed bilaterally and occurred in both sexes. In addition, this study documented substantial peripapillary choroid thickening during spaceflight, which has never been reported in a prospective study cohort population and which may be a contributing factor in spaceflight-associated neuro-ocular syndrome. Data collection on spaceflight missions longer than 6 months will help determine whether the duration of the mission is associated with exacerbating these observed changes in ocular structure or visual function.

Neuroretinal rim response to transient changes in intraocular pressure in healthy non-human primate eyes.

Optic nerve head (ONH) neuroretinal rim thickness, quantified as minimum rim width (BMO-MRW), is a sensitive measure for assessing early glaucomatous disease. The BMO-MRW is sensitive to transient fluctuations in intraocular pressure (IOP), but the time course over which BMO-MRW decreases and recovers with changes in IOP remains unknown. The goal of this study was to investigate the dynamics of BMO-MRW changes over 2-h periods of mild or moderate IOP elevation, and subsequent recovery, in healthy non-human primate eyes. Eight non-human primates were included in the study. For each animal, in two different sessions separated by at least 2 weeks, the anterior chamber IOP of one eye was maintained at either 25 mmHg or 40 mmHg for 2 h and, subsequently, at 10 mmHg for 2 h. For the duration of anterior chamber cannulation, optical coherence tomography (OCT) radial scans centered on the ONH were acquired every 5 min and used to quantify BMO-MRW. An exponential decay or rise to maximum function was used to determine the extent and rate of structural change. Additionally, Bruch's membrane opening (BMO) area, BMO height/displacement, and BMO-referenced anterior lamina cribrosa surface depth (BMO-ALCSD) were computed from radial scans. A circular scan was used to quantify retinal nerve fiber layer thickness (RNFLT) and circumpapillary choroid thickness. The primary results demonstrated that the BMO-MRW changed over an extended duration, while BMO displacement was rapid and remained stable with sustained IOP. The mean maximum predicted BMO-MRW thinning following 2 h of IOP elevation was significantly related to pressure (34.2 ± 13.8 µm for an IOP of 25 mmHg vs 40.5 ± 12.6 µm for 40 mmHg, p = 0.03). The half-life for BMO-MRW thinning was 21.9 ± 9.2 min for 25 mmHg and 20.9 ± 4.2 min for 40 mmHg, not significantly different between IOP levels (p = 0.76). Subsequently, after 2 h of IOP at 10 mmHg, all animals exhibited partial recovery of BMO-MRW with similar degrees of persistent residual thinning for the two IOP levels (21.5 ± 13.7 vs 21.0 ± 12.3 µm, p = 0.88). Similar to BMO-MRW, choroid thickness exhibited gradual thinning with IOP elevation and residual thinning following IOP reduction. However, there was no significant change in BMO area or BMO-ALCSD in either experimental session. The RNFLT gradually decreased over the duration of IOP elevation, with continued decreases following IOP reduction for the 40 mmHg session, resulting in total changes from baseline of -2.24 ± 0.81 and -2.45 ± 1.21 µm for 25 and 40 mmHg, respectively (p < 0.001). The sum of the results demonstrate that the ONH neural tissue is sensitive to changes in IOP, the effects of which are gradual over an extended time course and different for increased vs. decreased pressure. Understanding the duration over which IOP influences BMO-MRW has important implications for studies investigating the effects of IOP on the ONH. Additionally, individual variability in ONH response to IOP may improve our understanding of the risk and progression of disease.

Trauma-informed interventions versus control for cancer-risk behaviours among adults: rationale and design for a randomized trial.

BACKGROUND: Tobacco use, alcohol use, and sugar-sweetened beverage consumption are each associated with increased cancer-risk. Psychological trauma is a common experience and a key driver of these behaviours among adults. The primary aim of this study is to evaluate the effect of trauma-informed yoga, drumming, and psychoeducation compared to control on tobacco use, alcohol use, and sugar-sweetened beverage consumption among community-based adults. Secondary aims are to evaluate the effect of these interventions compared to control on psychological and physiological stress symptomology, social connection, and coping behaviour. METHODS: Recruitment for this single-blinded randomized trial began in April 2019 in the Faculty of Health Sciences at the University of Lethbridge. Adults who consumed tobacco, alcohol, or sugar-sweetened beverages in the past month and live in Lethbridge, Alberta are being recruited using ads placed in public spaces. Participants are randomly allocated to a 12-session group yoga class, 12-session group drumming class, a 12-session psychoeducation class, or control. Participants attend an appointment in-person to fill out an online questionnaire package, provide a saliva sample, and complete physical measures pre-intervention, and 1-month and 6-months post-intervention. DISCUSSION: This study provides a unique opportunity to compare the impacts of two trauma-informed body-based interventions to psychoeducation and control for cancer-risk behaviour among community-based adults. The findings can be used to develop trauma-informed group interventions to reduce cancer-risk behaviour in general populations. Results are expected in 2022. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov ISRCTN15583681 on 22 August 2019 (retrospectively registered).

Twenty-four hour ocular and systemic diurnal rhythms in children.

PURPOSE: Ocular diurnal rhythms have been implicated in myopia, glaucoma, diabetes, and other ocular pathologies. Ocular rhythms have been well described in adults; however, they have not yet been fully examined in children. The goal of this study was to investigate ocular and systemic diurnal rhythms over 24 h in children. METHODS: Subjects, ages 5 to 14 years (n = 18), wore a light, sleep, and activity monitor for one week to assess habitual sleep/wake patterns, then underwent diurnal measurements every 4 h for 24 h. Measurements included blood pressure, heart rate, body temperature, intraocular pressure (IOP), ocular biometry, and optical coherence tomography imaging. Saliva was collected for melatonin and cortisol analysis. Mean ocular perfusion pressure was calculated from IOP and blood pressure. Central corneal thickness, corneal power, anterior chamber depth, lens thickness, vitreous chamber depth, and axial length were determined from biometry. Total retinal thickness, retinal pigment epithelium (RPE) + photoreceptor outer segment thickness, photoreceptor inner segment thickness, and choroidal thickness were determined for a 1 mm diameter centred on the fovea. Subjects' amplitude and acrophase of diurnal variation for each parameter were determined using Fourier analysis, and mean acrophase was calculated using unit vector averaging. RESULTS: Repeated measures analysis of variance (ANOVA) showed that all parameters except anterior chamber depth exhibited significant variations over 24 h (p ≤ 0.005 for all). Axial length underwent diurnal variation of 45.25 ± 6.30 µm with an acrophase at 12.92 h, and choroidal thickness underwent diurnal variation of 26.25 ± 2.67 µm with an acrophase at 1.90 h. IOP was approximately in phase with axial length, with a diurnal variation of 4.19 ± 0.50 mmHg and acrophase at 11.37 h. Total retinal thickness underwent a significant diurnal variation of 4.09 ± 0.39 µm with an acrophase at 15.04 h. The RPE + outer segment layer was thickest at 3.25 h, while the inner segment layer was thickest at 14.95 h. Melatonin peaked during the dark period at 2.36 h, and cortisol peaked after light onset at 9.22 h. CONCLUSIONS: Ocular and systemic diurnal rhythms were robust in children and similar to those previously reported in adult populations. Axial length and IOP were approximately in phase with each other, and in antiphase to choroidal thickness. These findings may have important implications in myopia development in children.

Custom Optical Coherence Tomography Parameters for Distinguishing Papilledema from Pseudopapilledema.

SIGNIFICANCE: Causes of papilledema can be life-threatening; however, distinguishing papilledema from pseudopapilledema is often challenging. The conventional optical coherence tomography (OCT) scan for assessing the optic nerve often fails to detect mild papilledema. Our study suggests that parameters derived from volumetric OCT scans can provide additional useful information for detecting papilledema. PURPOSE: Optical coherence tomography analysis of the optic nerve commonly measures retinal nerve fiber layer thickness (RNFLT) along a 1.73-mm-radius scan path. This conventional scan, however, often fails to detect mild papilledema. The purpose of this study was to evaluate additional OCT-derived measures of the optic nerve head (ONH) and peripapillary retina for differentiating papilledema (all grades and mild) from pseudopapilledema. METHODS: Cirrus OCT ONH volume scans were acquired from 21 papilledema (15 mild papilledema), 27 pseudopapilledema, and 42 control subjects. Raw scan data were exported, and total retinal thickness within Bruch's membrane opening (BMO) plus RNFLT and total retinal thickness at the following eccentricities were calculated using custom algorithms: BMO to 250, 250 to 500, 500 to 1000, and 1000 to 1500 µm. Minimum rim width was calculated, and BMO height was measured from a 4-mm Bruch's membrane reference plane centered on the BMO. RESULTS: Retinal nerve fiber layer thickness from BMO to 250 µm, minimum rim width, and BMO height had significantly greater areas under the receiver operating characteristic curve than did conventional RNFLT for differentiating mild papilledema from pseudopapilledema (P < .0001) and greater sensitivities at 95% specificity. Using cutoff values at 95% specificity, custom parameters detected 10 mild papilledema patients, and conventional RNFLT detected only 1. Bruch's membrane opening heights above the reference plane were observed in papilledema only, although many papilledema cases had a neutral or negative BMO height. CONCLUSIONS: Using OCT volumetric data, additional parameters describing peripapillary tissue thickness, neuroretinal rim thickness, and ONH position can be calculated and provide valuable measures for differentiating mild papilledema from pseudopapilledema.