Giovanni Taibbi

The Effect of Microgravity on Ocular Structures and Visual Function: A Review

Ocular structural and functional changes, including optic disk edema and reduction of near visual acuity, have been recently described in some astronauts returning from long-duration space travels. It is hypothesized that ocular changes related to spaceflight may occur, in predisposed individuals, as a result of cephalad shift of body fluids, possibly leading to elevated intracranial pressure (ICP). Results from head-down bed-rest studies (used to simulate the effects of microgravity) and from parabolic flight experiments (used to produce transient periods of microgravity) indicate that ocular blood flow and intraocular pressure (IOP) may undergo changes in a low-gravity environment. Recent studies suggest that changes in translaminar pressure (i.e., IOP minus ICP) may be implicated in the pathophysiology of optic disk neuropathies. Because postural changes exert an effect on both IOP and ICP, the head-down bed-rest analog may also be used as a platform to characterize the relationship between IOP and ICP, and their reciprocal influence in the pathophysiology of conditions such as optic disk edema or glaucoma.

Effects of 30-Day Head-Down Bed Rest on Ocular Structures and Visual Function in a Healthy Subject

INTRODUCTIONnWe report ocular changes occurring in a healthy human subject enrolled in a bed rest (BR) study designed to replicate the effects of a low-gravity environment.nnnCASE REPORTnA 25-yr-old Caucasian man spent 30 consecutive days in a 6 degrees head-down tilt (HDT) position at the NASA Flight Analogs Research Unit. Comprehensive ophthalmologic exams, optic disc stereo-photography, standard automated perimetry (SAP), and optic disc Spectralis OCT scans were performed at baseline, immediately post-BR (BR+0), and 6 mo post-BR.nnnMAIN OUTCOME MEASURESnchanges in best-corrected visual acuity, intraocular pressure (IOP), cycloplegic refraction, SAP, and Spectralis OCT measures. At BR+0 KIOP was 11 and 10 mmHg in the right (OD) and left eye (OS), respectively (a bilateral 4-mmHg decrease compared to baseline); SAP documented a possible bilateral symmetrical inferior scotoma; Spectralis OCT showed an average 19.4 microm (+5.2%) increase in peripapillary retinal thickness, and an average 0.03 mm3 (+5.0%) increase in peripapillary retinal volume bilaterally. However, there were no clinically detectable signs of optic disc edema. At 6 mo post-BR, IOP was 13 and 14 mmHg in OD and OS, respectively, and the scotoma had resolved. Spectralis OCT measurements matched the ones recorded at baseline.nnnDISCUSSIONnIn this subject, a reduction in IOP associated with subtle structural and functional changes compared to baseline were documented after prolonged head-down BR. These changes may be related to cephalad fluid shifts in response to tilt. Further studies should clarify whether decreased translaminar pressure (i.e., the difference between IOP and intracranial pressure) may be responsible for these findings.

Ocular outcomes evaluation in a 14-day head-down bed rest study.

INTRODUCTIONnWe evaluated ocular outcomes in a 14-d head-down tilt (HDT) bed rest (BR) study designed to simulate the effects of microgravity on the human body.nnnMETHODSnHealthy subjects were selected using NASA standard screening procedures. Standardized NASA BR conditions were implemented (e.g., strict sleep-wake cycle, standardized diet, 24-hour-a-day BR, continuous video monitoring). Subjects maintained a 6° HDT position for 14 consecutive days. Weekly ophthalmological examinations were performed in the sitting (pre/post-BR) and HDT (in-bed phase) positions. Equivalency tests with optimal-alpha techniques evaluated pre/post-BR differences in best-corrected visual acuity (BCVA), spherical equivalent, intraocular pressure (IOP), Spectral-domain OCT retinal nerve fiber layer thickness (RNFLT), optic disc and macular parameters.nnnRESULTSn16 subjects (12 men and 4 women) were enrolled. Nearly all ocular outcomes were within our predefined clinically relevant thresholds following HDTBR, except near BCVA (pre/post-BR mean difference: -0.06 logMAR), spherical equivalent (-0.30 D), Tonopen XL IOP (+3.03 mmHg) and Spectralis OCT average (+1.14 μm), temporal-inferior (+1.58 μm) and nasal-inferior RNFLT (+3.48 μm). Modified Amsler grid, red dot test, confrontational visual field, and color vision were within normal limits throughout. No changes were detected on stereoscopic color fundus photography.nnnDISCUSSIONnA few functional and structural changes were detected after 14-d HDTBR, notably an improved BCVA possibly due to learning effect and RNFL thickening without signs of optic disc edema. In general, 6° HDTBR determined a small nonprogressive IOP elevation, which returned to baseline levels post-BR. Further studies with different BR duration and/or tilt angle are warranted to investigate microgravity-induced ophthalmological changes.

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

Purpose To compare ocular outcomes in healthy subjects undergoing 14- and/or 70-day head-down-tilt (HDT) bed rest (BR). Methods Participants were selected by using NASA standard screening procedures. Standardized NASA BR conditions were implemented. Subjects maintained a 6° HDT position for 14 and/or 70 consecutive days. Weekly ophthalmologic examinations were performed in the sitting (pre/post-BR only) and HDT positions. Mixed-effects linear models compared pre- and post-HDT BR observations between 14- and 70-day HDT BR in best-corrected visual acuity, spherical equivalent, intraocular pressure (IOP), Spectralis OCT retinal nerve fiber layer thickness, peripapillary and macular retinal thicknesses. Results Sixteen and six subjects completed the 14- and 70-day HDT BR studies, respectively. The magnitude of HDT BR–induced changes was not significantly different between the two studies for all outcomes, except the superior (mean pre/post difference of 14- vs. 70-day HDT BR: +4.69 μm versus +11.50 μm), nasal (+4.63 μm versus +11.46 μm), and inferior (+4.34 μm versus +10.08 μm) peripapillary retinal thickness. A +1.42 mm Hg and a +1.79 mm Hg iCare IOP increase from baseline occurred during 14- and 70-day HDT BR, respectively. Modified Amsler grid, red dot test, confrontational visual field, color vision, and stereoscopic fundus photography were unremarkable. Conclusions Seventy-day HDT BR induced greater peripapillary retinal thickening than 14-day HDT BR, suggesting that time may affect the amount of optic disc swelling. Spectralis OCT detected retinal nerve fiber layer thickening post BR, without clinical signs of optic disc edema. A small IOP increase during BR subsided post HDT BR. Such changes may have resulted from BR-induced cephalad fluids shift. The HDT BR duration may be critical for replicating microgravity-related ophthalmologic changes observed in astronauts on ≥6-month spaceflights.

Analysis by NASA's VESGEN Software of Vascular Branching in the Human Retina with a Ground-Based Microgravity Analog

PURPOSEnTargeted drug delivery to the ocular tissues remains a challenge. Biodegradable intraocular implants allow prolonged controlled release of drugs directly into the eye. In this study, we evaluated an anterior suprachoroidal polyurethane implant containing dexamethasone polyurethane dispersions (DX-PUD) as a drug delivery system in the rat model of endotoxin-induced uveitis (EIU).nnnMETHODSnIn vitro drug release was studied using PUD implants containing 8%, 20%, and 30% (wt/wt) DX. Cytotoxicity of the degradation products of DX-PUD was assessed on human ARPE-19 cells using 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) test. Short-term ocular biocompatibility of suprachoroidal DX-PUD implants was evaluated in normal rat eyes. Endotoxin-induced uveitis was then induced in rat eyes preimplanted with DX-PUD. Clinical examination was performed at 24 hours; eyes were used to assess inflammatory cell infiltration and macrophage/microglial activation. Cytokine and chemokine expression in the iris/ciliary body and in the retina was investigated using quantitative PCR. Feasibility of anterior suprachoroidal PUD implantation was also tested using postmortem human eyes.nnnRESULTSnA burst release was followed by a sustained controlled release of DX from PUD implants. By-products of the DX-PUD were not toxic to human ARPE-19 cells or to rat ocular tissues. Dexamethasone-PUD implants prevented EIU in rat eyes, reducing inflammatory cell infiltration and inhibiting macrophage/microglial activation. Dexamethasone-PUD downregulated proinflammatory cytokines/chemokines (IL-1β, IL-6, cytokine-induced neutrophil chemoattractant [CINC]) and inducible nitric oxide synthase (iNOS) and upregulated IL-10 anti-inflammatory cytokine. Polyurethane dispersion was successfully implanted into postmortem human eyes.nnnCONCLUSIONSnDexamethasone-PUD implanted in the anterior suprachoroidal space may be of interest in the treatment of intraocular inflammation.

Effect of Motion Artifacts and Scan Circle Displacements on Cirrus HD-OCT Retinal Nerve Fiber Layer Thickness Measurements

PURPOSEnTo evaluate the effect of scan circle displacements on retinal nerve fiber layer thickness (RNFLT) measurements in Cirrus HD-OCT scans with motion artifacts affecting the optic disc.nnnMETHODSnIn this cross-sectional study, 70 scans from 18 healthy eyes and 100 scans from 26 glaucomatous eyes were divided into 85 pairs, each composed by a scan with one motion artifact affecting the optic disc, and a scan from the same eye without motion artifacts. En face images underwent automated realignment, and horizontal/vertical scan circle displacements were determined. Multiple regression analysis evaluated the relationship between scan circle displacements and RNFLT change.nnnRESULTSnScans with motion artifacts showed similar displacements in healthy and glaucomatous eyes (P values ≥ 0.08). Average RNFLT and quadrants were relatively unchanged, while clock-hours showed more changes (e.g., in glaucomatous eyes, clock-hour-7 RNFLT was lower in scans with motion artifacts, P = 0.05). Scan circle displacements produced average RNFLT changes above test-retest variability in 3/85 cases (3.53%). Retinal nerve fiber layer thickness tended to decrease in sectors moved away from the disc and to increase in sectors closer to the disc (R(2) ≤ 0.40 and R(2) ≤ 0.22 in healthy and glaucomatous eyes, respectively). In healthy eyes, horizontal displacements ≥ 423 and 325 μm were associated with average and quadrant RNFLT changes above test-retest variability, respectively.nnnCONCLUSIONSnScan circle displacements occurred in all scans with motions artifacts affecting the optic disc. Average RNFLT and quadrants were more robust than clock-hours. Because motion artifacts may be difficult to detect, clinicians should carefully inspect en face OCT images for their presence and interpret clock-hour results cautiously.

Factors Affecting Cirrus-HD OCT Optic Disc Scan Quality: A Review with Case Examples

Spectral-domain OCT is an established tool to assist clinicians in detecting glaucoma and monitor disease progression. The widespread use of this imaging modality is due, at least in part, to continuous hardware and software advancements. However, recent evidence indicates that OCT scan artifacts are frequently encountered in clinical practice. Poor image quality invariably challenges the interpretation of test results, with potential implications for the care of glaucoma patients. Therefore, adequate knowledge of various imaging artifacts is necessary. In this work, we describe several factors affecting Cirrus HD-OCT optic disc scan quality and their effects on measurement variability.

Effects of short-term mild hypercapnia during head-down tilt on intracranial pressure and ocular structures in healthy human subjects

Many astronauts experience ocular structural and functional changes during long‐duration spaceflight, including choroidal folds, optic disc edema, globe flattening, optic nerve sheath diameter (ONSD) distension, retinal nerve fiber layer thickening, and decreased visual acuity. The leading hypothesis suggests that weightlessness‐induced cephalad fluid shifts increase intracranial pressure (ICP), which contributes to the ocular structural changes, but elevated ambient CO2 levels on the International Space Station may also be a factor. We used the spaceflight analog of 6° head‐down tilt (HDT) to investigate possible mechanisms for ocular changes in eight male subjects during three 1‐h conditions: Seated, HDT, and HDT with 1% inspired CO2 (HDT + CO2). Noninvasive ICP, intraocular pressure (IOP), translaminar pressure difference (TLPD = IOP‐ICP), cerebral and ocular ultrasound, and optical coherence tomography (OCT) scans of the macula and the optic disc were obtained. Analysis of one‐carbon pathway genetics previously associated with spaceflight‐induced ocular changes was conducted. Relative to Seated, IOP and ICP increased and TLPD decreased during HDT. During HDT + CO2 IOP increased relative to HDT, but there was no significant difference in TLPD between the HDT conditions. ONSD and subfoveal choroidal thickness increased during HDT relative to Seated, but there was no difference between HDT and HDT + CO2. Visual acuity and ocular structures assessed with OCT imaging did not change across conditions. Genetic polymorphisms were associated with differences in IOP, ICP, and end‐tidal PCO2. In conclusion, acute exposure to mild hypercapnia during HDT did not augment cardiovascular outcomes, ICP, or TLPD relative to the HDT condition.

Ophthalmological Evaluation of Integrated Resistance and Aerobic Training During 70-Day Bed Rest

INTRODUCTIONnWe evaluated ophthalmic changes in healthy individuals who underwent integrated resistance and aerobic training (iRAT) during 70-d 6° head-down tilt (HDT) bed rest (BR).nnnMETHODSnParticipants were selected using NASA standard screening procedures. Standardized NASA BR conditions were implemented. Subjects were randomly assigned to the iRAT protocol or no exercise during HDTBR. Weekly ophthalmic examinations were performed in the sitting (pre/post-BR only) and HDT (BR only) positions. Mixed-effects linear models compared pre- and post-HDTBR intraocular pressure (IOP), Spectralis OCT circumpapillary retinal nerve fiber layer (cpRNFL) thickness, and peripapillary retinal thickness observations between groups.nnnRESULTSnSix controls and nine exercisers completed the study. There was an overall effect of BR on our outcomes. Except Goldmann IOP (mean pre/post difference in controls and exercisers: -0.47 mmHg vs. +1.14 mmHg), the magnitude of changes from baseline was not significantly different between groups. There was a +1.38 mmHg and a +1.63 mmHg iCare IOP increase during BR in controls and exercisers, respectively. Spectralis OCT detected a +1.33 μm average cpRNFL thickness increase in both groups, and a +9.77 μm and a +6.65 μm peripapillary retinal thickening post-BR in controls and exercisers, respectively. Modified Amsler grid, red dot test, confrontational visual field, color vision, and stereoscopic fundus photography were unremarkable.nnnCONCLUSIONSnHDTBR for 70 d induced peripapillary retinal thickening and cpRNFL thickening without visible signs of optic disc edema. The magnitude of such changes was not different between controls and exercisers. A slight IOP increase during BR subsided post-BR. Further study should evaluate whether different physical exercise paradigms may prevent/mitigate the risk of space-related visual impairment.Taibbi G, Cromwell RL, Zanello SB, Yarbough PO, Ploutz-Snyder RJ, Godley BF, Vizzeri G. Ophthalmological evaluation of integrated resistance and aerobic training during 70-day bed rest. Aerosp Med Hum Perform. 2017; 88(7):633-640.

Correlation and Agreement Between Cirrus HD-OCT "RNFL Thickness Map" and Scan Circle Retinal Nerve Fiber Layer Thickness Measurements.

Purpose:To evaluate the correlation and agreement between optical coherence tomography (Cirrus HD-OCT) retinal nerve fiber layer (RNFL) thickness map and scan circle RNFL thickness measurements. Methods:ImageJ and custom Perl scripts were used to derive RNFL thickness measurements from RNFL thickness maps of optic disc scans of healthy and glaucomatous eyes. Average, quadrant, and clock-hour RNFL thickness of the map, and RNFL thickness of the areas inside/outside the scan circle were obtained. Correlation and agreement between RNFL thickness map and scan circle RNFL thickness measurements were evaluated using R2 and Bland-Altman plots, respectively. Results:A total of 104 scans from 26 healthy eyes and 120 scans from 30 glaucomatous eyes were analyzed. RNFL thickness map and scan circle measurements were highly reproducible (eg, in healthy eyes, average RNFL thickness coefficients of variation were 2.14% and 2.52% for RNFL thickness map and scan circle, respectively) and highly correlated (0.55⩽R2⩽0.98). In general, the scan circle provided greater RNFL thickness than the RNFL thickness map in corresponding sectors and the differences tended to increase as RNFL thickness increased. The width of the 95% limits of agreement ranged between 5.28 and 36.80 &mgr;m in healthy eyes, and between 11.69 and 42.89 &mgr;m in glaucomatous eyes. Conclusions:Despite good correlation between RNFL thickness map and scan circle measurements, agreement was generally poor, suggesting that RNFL thickness assessment over the entire scan area may provide additional clinically relevant information to the conventional scan circle analysis. In the absence of available measurements from the entire peripapillary region, the RNFL thickness maps can be used to investigate localized RNFL thinning in areas not intercepted by the scan circle.