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

Abstract

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.

Figure 1.. Method for Quantifying Optic Nerve Head Morphology

A. Thirty-degree scanning laser ophthalmoscopy image with radial scan pattern (green lines). B. The image shows segmentations of the internal limiting membrane (ILM, yellow line) and Bruch membrane (BM, red line), BM opening (BMO) points (orange dots), BMO reference (orange dashed line), cup reference (cyan dashed line) located 200 μm anterior to the BMO reference, minimum rim width (MRW, green lines), and 250 μm annulus extending from the BMO (gray shaded region) used to quantify total retinal thickness. The region corresponding to the optic cup is shaded (cyan).

Figure 2.. Changes in Peripapillary Total Retinal Thickness (TRT) Across Individual Study Participants at Approximately Flight Day 150

Increases in TRT above the predefined threshold for optic disc edema (19.4 μm; gray shading) were seen across both sexes and both eyes. Peripapillary TRT was quantified within an annular region extending from the Bruch membrane opening (BMO) to 250 μm (BMO-250).

Figure 3.. Association Between Smaller Optic Cup Size and Greater Increase in Total Retinal Thickness (TRT) During Spaceflight

The change in TRT measured on approximately flight day 150 showed inverse associations with preflight cup volume (A), preflight cup depth (B), and preflight cup width (C). The change was not associated with preflight cup-disc ratio (D). Data points for all eyes (n = 62) are shown, with linear regressions (solid lines) and 95% CIs (dashed lines). The shaded regions indicate the previously established TRT threshold (± 19 μm) for identifying optic disc edema. The horizontal line at 0 represents no change. Peripapillary TRT was quantified within an annular region extending from the Bruch membrane opening (BMO) to 250 μm (BMO-250).

Figure 4.. Body Weight and Body Mass Index vs Changes in Total Retinal Thickness (TRT) During Spaceflight

The change in TRT measured on approximately flight day 150 was not associated with preflight body weight (A) or preflight body mass index (B). Data points for all eyes (n = 62) are shown, with linear regressions (solid lines) and 95% CIs (dashed lines). The shaded regions indicate the previously established TRT threshold (± 19 μm) for identifying optic disc edema. The horizontal line at 0 represents no change. Body mass index was calculated as weight in kilograms divided by height in meters squared. Peripapillary TRT was quantified within an annular region extending from the Bruch membrane opening (BMO) to 250 μm (BMO-250).