Retinal microvasculature is a potential biomarker for acute mountain sickness

Purpose To use optical coherence tomography angiography (OCTA) to assess the pattern of changes in retinal and choroidal blood flow and structure in healthy volunteers who quickly went from sea level to a plateau and to determine the parameters associated with acute mountain sickness (AMS). Methods Forty-five individuals (89 eyes) were examined by OCTA and filled out the AMS questionnaire. One baseline examination was performed on the plain, followed by examinations at days 1, 3, and 5 after entering the plateau. Parameters were self-controlled to explore patterns of change, analyzed for correlation with AMS score, and modeled as a nomogram of AMS risk. Results On the plateau compared to the plain, vascular morphology showed dilated superficial macular retinal vessels and constricted deeper layers with increased vessel length density and fractal dimension; vessel density increased in all retinal strata and decreased in the choroidal macrovascular layer; and thickness increased except for a decrease in mean retinal thickness in the central macular sulcus. The rate of increase in retinal nerve fiber layer (RNFL) thickness in the inner and outer macular rings correlated with AMS score (r = −0.211). The nomogram showed moderate accuracy (AUC = 0.672) and consistency (C-index = 0.659) in assessing AMS risk. Conclusions In high-altitude hypoxia, retinal vessels dilate and distort, resulting in increased blood flow density and thickness. Increased RNFL thickness in the paracentral macula may be a marker of low AMS risk. Translational Relevance The changes in the retinal structure of the fundus can be used to assess the risk of developing AMS.

Patterns of Structural Changes in the Fundus Measured by Optical Coherence Tomography Angiography as Potential Markers of Acute Mountain Sickness

Background: Exposure to high-altitude conditions during flight or similar activities affects many aspects of visual function, which is critical not only for flight safety but for any altitude-related activity. We aimed to summarize the available literature pertaining to ocular changes during flight or equivalent short-term high-altitude exposure (e.g., hypobaric chamber, effortless ascent lasting ≤ 24 h) and to highlight future research priorities. Methods: Using the PubMed/MEDLINE and Web of Science/ISI Web of Knowledge databases with structured search syntax, we conducted a systematic review of the literature spanning a 40-year period (January 1, 1983, to October 10, 2023). Articles pertaining to ocular changes during flight or flight-equivalent exposure to altitude were retrieved. The reference lists of retrieved studies were also searched, and citations of these references were included in the results. Results: Of 875 relevant PubMed and ISI publications, 122 qualified for inclusion and 20 more were retrieved from the reference lists of initially selected records, for a total of 142 articles. Reported anterior segment changes included deterioration in tear film stability and increased dry eye incidence, increased corneal thickness, discomfort and bubble formation in contact lens users, refraction changes in individuals with prior refractive surgery, decreased intraocular pressure, and alterations in pupillary reaction, contrast sensitivity, and visual fields. Photoreceptor–visual pathway changes included alterations in both photoreceptors and neuro-transduction, as evidenced in dark adaptation, macular recovery time, reduction in visual field sensitivity, and optic neuritis (likely an element of decompression sickness). Retinochoroidal changes included increases in retinal vessel caliber, retinal blood flow, and choroidal thickness; central serous chorioretinopathy; and retinal vascular events (non-arteritic ischemic optic neuropathy, high-altitude retinopathy, and retinal vein occlusion). Conclusions: The effect of short-term high-altitude exposure on the eye is, in itself, a difficult area to study. Although serious impairment of visual acuity appears to be rare, ocular changes, including tear film stability, contact lens wear, central corneal thickness, intraocular pressure, contrast sensitivity, stability of refractive surgeries, retinal vessels, visual fields, and macula recovery time, should be considered in civilian aviators. Our report provides guidance to climbers and lowlanders traveling to altitude if they have pre-existing ocular conditions or if they experience visual symptoms while at altitude. However, key outcomes have been contradictory and comprehensive studies are scarce, especially those pertaining to the choroid and retina. Such studies could not only deepen our understanding of high-altitude ocular pathophysiology, but could also offer valuable information and treatment possibilities for a constellation of other vision-threatening diseases.

Impact of flight and equivalent short-term high-altitude exposure on ocular structures and function

Background As an autoimmune disease, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) often affects multiple organs, including the ocular system. This study aims to investigate differences in retinal thickness (RT) and retinal superficial vascular density (SVD) between patients with AAV and healthy controls (HCs) using optical coherence tomography angiography (OCTA). Currently, these differences are not clear. Methods A total of 16 AAV individuals (32 eyes) and 16 HCs (32 eyes) were recruited to this cross-sectional study conducted in the First Affiliated Hospital of Nanchang University from June 2023 to September 2023. The study protocol conformed with the tenets of the Declaration of Helsinki (as revised in 2013). Each image observed by OCTA was divided into 9 regions using the Early Treatment Diabetic Retinopathy Study (ETDRS) subzones as a guide. Results In the full layer, the RT of AAV patients was found to be significantly reduced in the inner superior (IS, P<0.001), outer superior (OS, P=0.003), inner temporal (IT, P=0.003), and outer temporal (OT, P<0.001) regions; inner RT was significantly lower in the IS (P=0.006), OS (P<0.001), inner nasal (IN, P=0.005), outer nasal (ON, P<0.001), and center (C, P=0.01) regions than that in HCs. Outer RT of AAV patients showed a reduction in the IS (P<0.001), as well as IT (P=0.008), and OT (P<0.001) regions. No statistically significant differences were seen in the different subregions in other different layers (P>0.05). Only the inner inferior (II) and outer inferior (OI) regions of SVD in AAV patients did not differ significantly from controls. All other regions showed a reduction in SVD. The details are as follows: IS (P<0.001), OS (P<0.001), IT (P=0.005), OT (P<0.001), IN (P<0.001), ON (P<0.001), and C (P=0.003). According to receiver operating characteristic (ROC) curve analysis, the full IS region [area under the curve (AUC): 0.8892, 95% confidence interval (CI): 0.8041–0.9742, P<0.001] had the highest diagnostic value for AAV-induced reduction in RT. The IS (AUC: 0.9121, 95% CI: 0.8322–0.9920, P<0.001) region was also the most sensitive to changes in SVD of AAV individuals. In addition, we found that SVD in the IN region (r=−0.4224, 95% CI: −0.6779 to −0.0757, P=0.02) as well as mean visual acuity (r=−0.3922, 95% CI: −0.6579 to −0.0397, P=0.03) of AAV patients were negatively correlated with disease duration. However, we did not find an association between SVD and RT in this study. Conclusions The findings from OCTA indicated a reduction in RT and SVD among patients with AAV. OCTA allows for the evaluation of AAV-related ocular lesions and holds promise for monitoring of disease progression through regular evaluations.

Retinal thickness and microvascular alterations observed by optical coherence tomography in antineutrophil cytoplasmic antibody-associated vasculitis: a cross-sectional study

Cerebral hypoxia is a serious consequence of several cardiorespiratory illnesses. Measuring the retinal microvasculature at high altitude provides a surrogate for cerebral microvasculature, offering potential insight into cerebral hypoxia in critical illness. Additionally, while sex-specific differences in cardiovascular diseases are strongly supported, few have focused on differences in ocular blood flow. We evaluated the retinal microvasculature in males (n=11) and females (n=7) using functional optical coherence tomography at baseline (1,130m) (Day 0), following rapid ascent (Day 2) and prolonged exposure (Day 9) to high altitude (3,800m). Retinal vascular perfusion density (rVPD; an index of total blood supply), retinal thickness (RT; reflecting vascular and neural tissue volume) and arterial blood were acquired. As a group, rVPD increased on Day 2 vs. Day 0 (p<0.001) and was inversely related to PaO2 (R2=0.45; p=0.006). By Day 9, rVPD recovered to baseline, but was significantly lower in males vs. females (p=0.007). RT was not different on Day 2 vs. Day 0 (p>0.99) but was reduced by Day 9 relative to Day 0 and Day 2 (p<0.001). RT changes relative to Day 0 were inversely related to changes in PaO2 on Day 2 (R2=0.6; p=0.001) and Day 9 (R2=0.4; p=0.02). RT did not differ between sexes. These data suggest differential time course and regulation of the retina during rapid ascent and prolonged exposure to high altitude and are the first to demonstrate sex-specific differences in rVPD at high altitude. The ability to assess intact microvasculature contiguous with the brain has widespread research and clinical applications.

Functional optical coherence tomography at altitude: retinal microvascular perfusion and retinal thickness at 3,800 meters

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Functional optical coherence tomography at altitude: retinal microvascular perfusion and retinal thickness at 3,800 meters