CASE REPORT
Ultramarathon-Induced Bilateral Corneal Edema:A Case Report and a Review of the Literature
Majid Moshirfar . Yanning Ding . Yasmyne Ronquillo . Orry C. Birdsong .
Michael S. Murri
Received: February 6, 2018 / Published online: March 13, 2018� The Author(s) 2018. This article is an open access publication
ABSTRACT
Ultramarathon-associated corneal edema is arare phenomenon. We report a case of a patientwho presented with bilateral corneal edemafollowing an ultramarathon. The corneal edemaresolved without sequelae 48 h later. Theauthors hypothesize that the additive effect ofenhanced glycolysis, an increased lactate levelin the aqueous humor, and oxidative stressalters the normal endothelial regulation of thecornea and leads to corneal edema.
Keywords: Corneal edema; Ultramarathon;Visual impairment
INTRODUCTION
Corneal edema is not commonly seen as a resultof athletic activities. In a survey-based investi-gation, 173 ultramarathon runners describedtheir visual impairment as painless blurredvision that resolved spontaneously 24–48 hafter they stopped running. Corneal edema wasconfirmed via slit lamp examination in eight ofthe runners [1]. This phenomenon was alsoreported in a cyclist in a 161-km mountain bikerace [2]. Long-distance endurance sports mayhave an impact on the cornea and affect itsnormal mechanism of maintaining trans-parency. For the purpose of this review, anultramarathon is defined as any running com-petition longer than 26.2 miles (42.2 km), withmost races falling between 40 and 100 miles(70–160 km). We present a case of a patient withbilateral corneal edema occurring immediatelyafter an ultramarathon, and hypothesize on thepossible underlying mechanisms.
CASE REPORT
A 44-year-old white man experienced painlessbilateral blurring of vision during and after anultramarathon event in Park City, Utah, in April2011. He noticed the visual impairment pri-marily in the right eye during the last few hoursof the ultramarathon and presented to ourclinic 5 h after completion of the event. This
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M. Moshirfar (&) � Y. Ding � Y. Ronquillo �O. C. BirdsongHDR Research Center, Hoopes Vision, Draper, UT,USAe-mail: [email protected]
M. MoshirfarDepartment of Ophthalmology and Visual Sciences,John A. Moran Eye Center, University of UtahSchool of Medicine, Salt Lake City, UT, USA
M. S. MurriBaylor College of Medicine, Houston, TX, USA
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https://doi.org/10.1007/s40123-018-0125-y
was his first ultramarathon and he had not hadany similar episodes of visual impairment inprevious athletic activities. Past medical historyincluded hyperlipidemia, controlled by ator-vastatin (Lipitor). Family, social, surgical andophthalmologic histories were non-contribu-tory. He presented to the clinic the eveningafter the event. The patient involved providedwritten informed consent to having his dataused for research purposes, in accordance withthe tenets of the Declaration of Helsinki.
On eye examination, the patient had visualacuity of 20/200 OD and 20/30 OS. Intraocularpressure was 17 mmHg OD and 18 mmHg OS.Extraocular muscle movements were intact. Theorbits and eyelids revealed no evidence oftrauma. On slit lamp examination, the right eyehad diffuse 3? corneal edema with a few Des-cemet’s folds (Figs. 1 and 2) while the left eyehad trace to 1? corneal edema located on thenasal periphery of the cornea and dissipated atthe temporal side. The conjunctivae had noinjection and there was no corneal epithelialabrasion in either eye. The anterior chamber,iris and lens were normal in both eyes. Therewas no evidence of pigment dispersion. A dila-ted pupil fundus exam revealed a normal opticnerve, vasculature and macula on the left side,and only red reflex was appreciated in the righteye due to corneal edema.
The patient was prescribed prednisoloneacetate 1% ophthalmic suspension QID for botheyes. His vision subjectively recovered to his
baseline 12 h later, and an eye exam performed48 h after the episode showed complete recov-ery of both corneas without sequelae.Endothelial microscopy/counting was notperformed.
DISCUSSION
Ultramarathon events have been growing inpopularity over the past decade [3]. Theseevents usually take place in a mountainous areaon a course mixed with trails, tough road andsignificant elevation changes [4]. Men’s andwomen’s records for the Western States Endur-ance Run, which is 161 km, are 14:46:44 and16:47:19, respectively [5]. Many runners take24–36 h to finish these races. As Hoeg et al.mentioned in their investigation, environmen-tal stimuli increase the metabolic rate of thecornea [1]. During the race, the corneal epithe-lium must endure wind, temperature changesand enhanced ultraviolet (UV) light exposure,and cope with decreased oxygen tension athigher elevations. Unlike track runners, whoanticipate no obstacles ahead, ultramarathonrunners must constantly use their eyes to selectthe best path. This visual attention reduces thespontaneous blink rate [6], which intensifies thephysical challenge to the corneal epithelium.Cells cope with environmental stress such asthermal changes with enhanced glycolysis [7].Certain mechanisms involving cellular damagerepair rely more upon glycolysis than uponoxidative phosphorylation [8]. When the cor-neal epithelium increases glycolysis in thisconstant running state, lactate productionincreases. Bonanno explained the movement oflactate across the epithelium to the aqueoushumor in the following pattern [9]: (a) lactate istransferred to the stroma by the lactate-protoncotransporter located at the membrane ofepithelial cells [10]; (b) lactate moves across thestroma by simple diffusion down the gradient tothe membrane; (c) lactate-proton cotransporterand sodium-dependent lactate transporterfacilitate the entry of lactate into endothelialcells; (d) lactate then exits the endothelialmembrane by lactate-proton cotransporter toenter the anterior chamber [11]. Stromal lactate
Fig. 1 Diffuse corneal edema and Descemet’s folds inright eye
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Fig. 2 a OCT of right eye showing diffuse thickening secondary to corneal edema, affecting the epithelium as well. b Totalcorneal thickness. c Epithelial corneal thickness. d Stromal corneal thickness
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accumulation has been proven to be responsiblefor corneal edema, because increased osmolalityattracts water [12]. Elevated lactate levels weredetected in the blood of amateur ultramarathonrunners during a 100-km run [13]. Elevation ofblood lactate could cause increased lactate inthe aqueous humor, which would in turndecrease the lactate gradient between endothe-lial cells and aqueous humor, thus impairingthe facilitated transport of lactate to the
anterior chamber. We agree with Hoeg et al. [1]that this accumulation of lactate caused byincreased production and decreased excretion isone of the underlying mechanisms of the acutecorneal edema induced by ultramarathon run-ning (Fig. 3).
There are other potential causes of cornealedema during ultramarathons. High altitudecauses hypoxia and increased exposure to UVlight, and is known to induce an increase in
Fig. 3 Possible pathophysiologic mechanisms that may result in corneal edema in individuals during an ultramarathon(MCT monocarboxylate cotransporter or lactate cotransporter, Lac- lactate, H? hydrogen, H2O water)
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central corneal thickness [14]. Hypoxia-inducedcorneal edema has been shown quantitativelyin multiple studies in contact lens wearers[15, 16]. In a study investigating how UVA-in-duced oxidation affects different corneal cells,Zinflou et al. found that corneal epithelial cellscan adapt more quickly than endothelial cells[17]. The mechanism through which epithelialcells limit UVA-induced toxicity likely involvesenhanced glycolysis to create more ATP. On theother hand, the susceptibility of endotheliumto UVA can damage the pump function of theendothelium, which is the driving force inmoving water out of the stroma [9]. Our patientexperienced his event at high altitude (ParkCity, UT, USA, roughly 7000 feet elevation) andendured relatively distinct temperature changes(26.8–37.3 �C). Both could be contributing fac-tors to the development of his corneal edema.The definite cause of the difference in severityof corneal edema in our patient’s eyes isunknown, but we suggest that it may be due todifferent degrees of exposure to external irri-tants such as UV light and wind.
Other contributing factors causing cornealedema could include (a) participants wearingsoft contact lenses; (b) participants with priorcorneal refractive surgery changing the originalstructure of the anterior layers of the cornea,which could affect the metabolism and excre-tion of lactate into the aqueous humor; and(c) corneal endothelial dystrophy altering theregulation of corneal hydration.
After reviewing limited literature concerningthis matter, we hypothesize that patients whowear soft contact lenses (especially with highercorrection), have silent guttata and subclinicalendothelial dystrophies, have a history of cor-neal transplantation, suffer from dry eye, orhave had corneal refractive surgery such asLASIK have a higher risk of developing cornealedema during ultramarathon events.
Eye protection should be the most effectivemethod for preventing corneal edema duringlong-endurance sports, since it provides shield-ing from wind and UV light. Administration oftopical 5% hypertonic sodium chloride canenhance corneal clarity in the event of cornealedema. Rest or closure of the eyes would beideal but is probably not realistic during the
competition. Since dehydration can furtherincrease the blood lactate level, adequatehydration is advised.
CONCLUSION
Ultramarathon-induced corneal edema is a raremultifactorial phenomenon. The additive effectof enhanced glycolysis, decreased lactateexcretion to the aqueous humor, ambient tem-perature changes, hypoxia, and oxidative stresscaused by exposure to UV light can impact thenormal endothelial regulation of the corneaand may lead to corneal edema. Inter-subjectvariability may be the result of varying meta-bolic rates and endothelial pump function, aswell as membrane transporter efficiency.
ACKNOWLEDGEMENTS
Funding. This study was funded by anunrestricted grant from Research to PreventBlindness (RPB), 360 Lexington Avenue, 22ndFloor, New York, NY, 10017. No support wasreceived for the publication of this article.
Authorship. All named authors meet theInternational Committee of Medical JournalEditors (ICMJE) criteria for authorship for thismanuscript, take responsibility for the integrityof the work, and have given final approval forthe version to be published.
Disclosures. Majid Moshirfar, YanningDing, Yasmyne Ronquillo, Orry C. Birdsong,and Michael S. Murri have nothing to disclose.
Compliance with Ethics Guidelines. Thepatient involved provided written informedconsent to having his data used for researchpurposes, in accordance with the tenets of theDeclaration of Helsinki.
Open Access. This article is distributedunder the terms of the Creative CommonsAttribution-NonCommercial 4.0 InternationalLicense (http://creativecommons.org/licenses/
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by-nc/4.0/), which permits any non-commercial use, distribution, and reproductionin any medium, provided you give appropriatecredit to the original author(s) and the source,provide a link to the Creative Commons license,and indicate if changes were made.
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