Sonographic Evaluation of Spaceflight Effects on the Eye and Orbit

A. Sargsyan1, D. Bedi2, R. Ernst2, K. Garcia1, M. Van Baalen3, M. Foy1, S. Mason7, M. Wear1, U. Straube4, V. Damann4, K. Shimada5, J-M. Comtois6, D. Ebert1, D. Hamilton1, W. Tarver2, S. Hart2, S. Moynihan2, T. Taddeo2

84th Annual Scientific Meeting, AsMA, Chicago 2013

Disclosure Information84th AsMA Annual Scientific Meeting

Ashot E. Sargsyan

No financial relationships to disclose

Will not discuss off-label use and/or investigational use

• New/advanced protocol and measurement/grading techniques

Purpose

To review selected parameters derived from eye and orbit sonography in astronauts using new quantitative and qualitative techniques

Introduction• High-definition eye/orbit sonographic protocol

is part of a battery of monitoring tests for use in all mission phases including flight

• Only sporadic evidence exists in peer-reviewed literature, with low-fidelity imaging

• No standards or applicable evidence-based guidelines/criteria available

• Own cohort data are to be used

Materials and Methods: Subjects

International Space Station and Shuttle crewmembers

Average Age (Years)

N

Female 46.4 7

Male 48.7 35

Materials and Methods: Equipment

•Early phase: – HDI-5000 multipurpose

ultrasound system (ATL/Philips Medical Systems, WA, USA)

•Majority:– Pre- and post-flight data: HD-15

multipurpose ultrasound system (Philips Medical Systems, WA, USA)

– In-flight data: Vivid Q multipurpose ultrasound system (General Electric, USA)

• High-frequency (12 MHz) linear array probes

• DICOM image analysis software Prosolv Cardiovascular (Fujifilm, USA)

“…the rig we used to measure how Tom Marshburn's heart is changing and adapting without gravity… Photograph by: Chris Hadfield, @Cmdr_Hadfield, Twitter

Materials and Methods: Timing

Standardized protocol:

•Pre-flight : Launch – (up to) 360d•In-flight: Launch +30d; Launch +90d; Landing - 30d•Post-flight: Landing + 3-7d

Materials and MethodsStandardized protocol Parameters

PARAMETER Exp. Range; units

1 US Optic Nerve Sheath Diameter (US ONSD) 0.4 – 1.0 cm2 US Optic Nerve Diameter (US OND) 0.24 - 0.6 cm3 US Globe Flattening Grades 0, 1, 2, 34 US Disc Elevation Grades 0, 1, 2, 35 Optic Nerve Sheath Hypoechogenicity Grades 0, 1, 2, 36 Optic Nerve Sheath Inhomogeneity Grades 0, 1, 2, 37 A-P Diameter (2D US Biometry) 2.10 – 2.70 cm8 ON tortuosity Grades 0, 1, 2, 39 Asymptomatic pathology (Eye and Orbit) Varies

Materials and MethodsStandardized protocol

Standard Views 1. Sagittal Antero-posterior Globe View

2. Sagittal Oblique View - Lateral 3. Axial Antero-posterior Globe View4. Axial Oblique View through upper lid 5. Axial Lateral View  

Additional /AlternativeViews

1. Sagittal Oblique View - Medial2. Axial Oblique View through lower lid3. Other views as clinically indicated or informative

Optic Nerve Sheath Diameter (ONSD) measurement

Technique and Quality Criteria for ONSD measurement

• Near-axial plane, forward gaze• No lens in view• Image plane intersects disc center (ON

penetration point), ie, “dark meets dark”)• Clear differentiation of ON proper and

arachnoid – “dark stripe” technique not acceptable

• Structure of the arachnoid layer must be visible• Measure at 3-4mm from vitreo-retinal interface• Measure perpendicular to the ON axis • Measure bilaterally and in 2+ image frames • For ONSD monitoring, review prior studies

US inter-measurer reliabilitySpearman Correlation

OD OS Cyclop3 4 5 3 4 5 3 4 5

0.92 0.94 0.89 0.92 0.94 0.94 0.91 0.93 0.90Concordance Correlation Coefficient

OD OS Cyclop3 4 5 3 4 5  3 4 5

0.91 0.92 0.88 0.91 0.93 0.92 0.85 0.89 0.86

No significant effects for side, flight phase, or time between tests.

Results: Preflight ONSD Distribution

ONSD Across Mission Phases

Preflight ONSD vs. VIIP ClassCutoff 0.6 0.65 0.7

Class 1-4

Sensitivity 0.82 (0.48,0.97) 0.55 (0.25, 0.82) 0.45 (0.18, 0.75)

Specificity 0.6 (0.17, 0.93) 1.00 (0.46,1.00) 1.00 (0.46, 1.00)

Class 2-4

Sensitivity 0.89 (0.51, 0.99) 0.67 (0.31, 0.91) 0.56 (0.23, 0.85)

Specificity 0.57 (0.20, 0.88) 1.00 (0.56, 1.00) 1.00 (0.56, 1.00)

Class 3-4 (disk edema present)

Sensitivity 1.00 (0.40, 1.00) 1.00 (0.40, 1.00) 0.75 (0.22, 0.99)

Specificity 0.42 (0.16, 0.71) 0.82 (0.48, 0.97) 0.83 (0.51, 0.97)

Preflight ONSD vs. VIIP Class (32 ISS astronauts)

Globe Flattening

Globe Flattening• The most ubiquitous ultrasound finding in “cases”• Grades 1-3 in > 40% in ISS crew post flight (57% at some point)• Grade 2-3 in ~12% in at least one eye at some point (10% by MRI)

• Present in: 10/12 crewmembers with ΔCR ≥0.5D

90% of ONSD increase100% in those with choroidal folds8/8 of disc edema

Grade 1 is transient in several cases, may represent normal (anatomical variants or physiological response)

Globe flattening appears to differ in intensity and character; choroidal engorgement and full-thickness globe flattening are two contributing mechanisms

The reliability of this parameter is not yet examined

Globe Flattening: Pre/In/Post

AP Diameter Across Mission Phases

AP Diameter/Refractive Error

AP Diameter vs. Axial Length

Concordance Correlation: 0.66

Spearman Correlation: 0.90

Forward Work• Continued review and analysis, correlation with

clinical data, MRI, OCT, etc• Quality and transferability assurance • Peer review • Transfer of methodology to investigator teams• Inter-modality analysis (US vs MRI; US vs. optical

biometry etc.)• Classification and quantification of flattening• Quantification of sheath structure• Reconciliation of methodology with “terrestrial”

authors – ONSD etc.

Conclusions

1. Standardized protocol appears sound and consistent

2. Own evidence / cohort approach for ONSD appears to be effective, method is reliable and accurate

3. Selected parameters fit well in the clinical approach to VIIP and address; recommend continued use