Ocular Deformations in Spaceflight-Associated Neuro-Ocular Syndrome and Idiopathic Intracranial Hypertension

Abstract

Purpose: Spaceflight-associated neuro-ocular syndrome (SANS) shares several clinical features with idiopathic intracranial-hypertension (IIH), namely disc edema, globe-flattening, hyperopia, and choroidal folds. Globe-flattening is caused by increased intracranial pressure (ICP) in IIH, but the cause in SANS is uncertain. If increased ICP alone causes SANS, then the ocular deformations should be similar to IIH; if not, alternative mechanisms would be implicated.

Methods: Using optical coherence tomography (OCT) axial images of the optic nerve head, we compared "pre to post" ocular deformations in 22 patients with IIH to 25 crewmembers with SANS. We used two metrics to assess ocular deformations: displacements of Bruch's membrane opening (BMO-displacements) and Geometric Morphometrics to analyze peripapillary shape changes of Bruch's membrane layer (BML-shape).

Results: We found a large disparity in the mean retinal nerve-fiber layer thickness between SANS (108 um; 95% confidence interval [CI] = 105-111 um) and IIH (300 um; 95% CI = 251-350.1 um). The pattern of BML-shape and BMO-displacements in SANS were significantly different from IIH (P < 0.0001). Deformations in IIH were large and preponderantly anterior, whereas the deformations in SANS were small and bidirectional. The degree of disc edema did not explain the differences in ocular deformations.

Conclusions: This study showed substantial differences in the degree of disc edema and the pattern of ocular deformations between IIH and SANS. The precise cause for these differences is unknown but suggests that there may be fundamental differences in the underlying biomechanics of each consistent with the prevailing hypothesis that SANS is consequent to multiple factors beyond ICP alone. We propose a hypothetical model to explain the differences between IIH and SANS based on the pattern of indentation loads.

Figure 1.

Twenty degree transverse axial optical coherence tomography (OCT) showing the placement of 20 equidistant “semi-landmarks” (landmarks that outline a curved structure) along Bruch's membrane layer (BML) in a patient with resolved papilledema (top, yellow points, “pre”-like) and papilledema (middle, red points, “post”). Both images (bottom inset) were superimposed and registered by aligning Bruch's membrane opening (BMO) along the vertical white lines and superimposing the reference points (a and b) located 2 mm from the BMO. Positional displacement of the BMO is measured at the midsection (bidirectional white arrow) of the yellow and red lines.

Figure 2.

Displacements of Bruch's membrane opening (BMO, from pre to post condition) for each eye sorted in order of magnitude and direction. A positive shift along the ordinate indicates that the “post” BMO-position relative to the “pre” was displaced toward the vitreous, negative shifts are displaced away from the vitreous. (A1) Includes the eyes from the entire idiopathic intracranial hypertension (IIH) cohort; (A2) is a subgroup of A1 with “mild papilledema” (i.e. Grade 1–2, mean RNFL ≤200 µm); (B3) includes the eyes from all of the crewmembers with spaceflight-associated neuro-ocular syndrome (SANS); (B4) is a subgroup of B3 with more “advanced SANS” (i.e. optic disc edema, choroidal folds, or TRT ≥40 um). Grey bar along the abscissa marks a “nil” zone with BMO-displacements between 18.5 to +18.5 µm considered to be insignificant. The inflection between anterior and posterior displacements is marked by a small grey vertical line on the abscissa. The associated table summarizes the probabilities, frequencies, and per cent ratios of anterior to posterior BMO-displacements for each group. BMO, Bruch's membrane opening; IIH, idiopathic intracranial hypertension; SANS, spaceflight-associated neuro-ocular syndrome.

Figure 3.

Geometric morphometric consensus (mean) shape deformations of Bruch's membrane layer (magnified 5 times) among patients with idiopathic intracranial hypertension (IIH) and crewmembers with spaceflight-associated neuro-ocular syndrome (SANS). (a) Consensus shapes of patients with IIH and papilledema (red solid line, “post”) and resolved papilledema (black dashed line, “pre”). (b) Consensus shapes of a subgroup with “mild” (Grade 1–2, mean RNFL <200 µm) papilledema (solid red line) and resolved mild papilledema (dashed black line). (c) Consensus shape comparison of crewmembers with SANS preflight (dashed black line) and inflight (solid red line). (d) Preflight-inflight consensus shapes from a subgroup of crewmembers with “advanced SANS” (only those with choroidal folds, disc edema, or Δ TRT >40 µm). (e) Preflight-inflight consensus shapes from those crewmembers’ eyes with anterior BMO-displacements (>18.5 µm). (f) Preflight-inflight consensus shapes from those crewmembers’ eyes with posterior BMO-displacements of <−18.5 µm.

Figure 4.

Summarizes the differences in ocular deformations between IIH (A) and SANS (B). We speculate on how indentation loads may hypothetically interact. (A)The mechanism in IIH is well understood and consequent to a concentrated retrolaminar indentation load caused by a large rise in ICP and retrolaminar tissue pressure, much greater in most cases to any increase in the prelaminar tissue pressure caused by swelling of the optic nerve head. (B) The mechanism in SANS remains uncertain; however, it is likely that ICP alone does not explain the anterior and posterior pattern of ocular deformations. We speculate that there may be a dynamic interaction between two types of loads. (B1) A mild retrolaminar indentation load akin to a IIH (caused by intracranial fluid shifts with a low grade elevation in the ICP or perioptic CSF sequestration or both) and (B2) a peripapillary indentation load that spares the BMO possibly caused by the combined effects of orbital-ocular fluid shifts that expands the choroid and possibly increases orbital tissue pressure. The direction of the ocular deformation, if any, is determined by the relative magnitude of each load and individual factors that may depend on gender, the material properties of the load bearing structures (e.g. sclera, lamina cribrosa, or optic nerve sheath) and structural anatomy (e.g. anatomic communication between the cranial-perioptic CSF compartments and the choroidal geometry).^, BML, Bruch's membrane layer; BMO, Bruch's membrane opening; CSF, cerebrospinal fluid; ICP, intracranial pressure; IIH, idiopathic intracranial hypertension; IOP, intraocular pressure; PLTP, prelaminar tissue pressure; RIL, retrolaminar tissue pressure; PIL, peripapillary indentation load; SANS, spaceflight-associated neuro-ocular syndrome.