By Evan Carr, DO, Jake Young, MD, and Robert H. Rosa, MD
Edited by Ahmad A. Aref, MD, MBA
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Following a visit to rheumatology for recent intermittent blurry vision, fatigue, and other nonspecific symptoms, Henry Humphrey* was referred to us for potential giant cell arteritis (GCA). Despite these symptoms, he lacked the classic GCA presentation, and his examination was benign. This led us to believe that he most likely did not have GCA, and he was scheduled for a follow-up exam in three weeks.
Two weeks later, the 65-year-old returned, troubled by the sudden onset of blurry vision in his left eye unrelated to his previous symptoms. He had no relevant medical history—and excluding his recent referral for potential GCA—he had no previous ocular history or trauma that would account for this acute change in vision.
We Get a Look
During this second exam, Mr. Humphrey’s BCVA was 20/30 in his right eye and 20/60 in his left—a decrease from 20/20 in both eyes two weeks earlier. His IOP was 17 mm Hg in his right eye and 19 mm Hg in his left. His pupils were isocoric, there was no afferent pupillary defect, and his ocular motility was full in both eyes.
The slit-lamp examination revealed diffuse stromal edema with Descemet membrane folds, diffuse microcystic edema, and a mild cataract in his left eye. The examination of his right eye was normal.
On Second Thought
It was apparent that Mr. Humphrey’s clinical findings were a result of corneal edema. Given his unremarkable history, our differential diagnosis was initially broad. His lack of epithelial involvement and systemic symptoms lowered our suspicion for traumatic or infectious causes. In the setting of a normal IOP and no recent surgery, corneal edema secondary to acute angle-closure glaucoma was also less likely.
This narrowed our focus to causes of endothelial dysfunction, which still included a vast array of drug-induced, infectious, toxic, systemic, and idiopathic causes.1
After considering the objective information at hand, we decided to return to the subjective and ask Mr. Humphrey a few more questions. We were quickly reminded that the patient’s history may be more than the means to a diagnosis; it can be the diagnosis itself.
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BEFORE TREATMENT. These images of the patient’s left eye show (1A) Descemet membrane folds (in slit beam) and microcystic edema (right of slit beam) in right and left panels. (1B) Descemet membrane folds and stromal edema in right and left panels. (Dotted blue oval = microcystic edema in corneal epithelium.)
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BEFORE AND AFTER. The left eye (2) prior to treatment and (3) at day 3 after treatment initiation, when we noted (3A) resolution of microcystic corneal epithelial edema, with subtle Descemet membrane folds and linear stromal opacities. Enlarged (40×) images show (3B) resolving Descemet membrane folds and (3C) linear stromal opacities in the setting of resolving stromal edema.
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Getting Into the Weeds
On further questioning, Mr. Humphrey informed us that the morning before his vision became blurred, he was tending to some unsightly weeds in his wife’s garden, and he unintentionally rubbed his left eye. A quick literature search of plant-induced endothelial dysfunction unearthed the culprit of Mr. Humphrey’s acute symptoms.
Plants in the Asclepias genus (milkweed) are globally distributed. While they serve an ornamental purpose and are often planted in gardens to attract butterflies, they are known causes of death among open-range grazing animals due to the production of compounds called cardenolides, or cardiac glycosides. These toxins protect plants from predation; in humans, they have a cardiotonic effect by binding to the integral membrane protein of the sodium–potassium adenosine triphosphatase (Na+/K+–ATPase) pump and inhibiting its activity.2,3
Pathogenesis
Corneal transparency is maintained through the creation of a deturgesced state by the corneal endothelial cell layer. Activity of the Na+/K+–ATPase pump expressed in the basolateral membrane of endothelial cells promotes fluid egression from a relatively hypo-osmotic corneal stroma to a relatively hyperosmotic anterior chamber.4 Cardiac glycosides concentrated in the latex of plants of the Asclepias genus have the ability to penetrate a cornea that has an intact epithelium and effectively inhibit Na+/K+–ATPase activity in the corneal endothelium, thus inducing corneal stroma edema.2-4
Management
Treatment and resolution of stromal edema caused by milkweed species is not well reported or studied. The use of topical steroids is likely important, as they not only aid in the reduction of ocular inflammatory symptoms, such as conjunctival injection, but also have been shown to increase the activity of the Na+/K+–ATPase pump.5 In the presence of altered cellular morphology secondary to endothelial dysfunction, this increase in pump activity can generate significant compensation for an otherwise inhibited endothelium.
Of note: the use of steroids in the setting of plant-induced toxicity is not ubiquitous, however. One case resolved with the use of artificial tears alone after 48 hours.2
Our treatment regimen consisted of tobramycin/dexamethasone, ofloxacin, and hypertonic saline; this mimicked the management in a case of toxicity related to exposure to A. physocarpa.6 Mr. Humphrey responded well: we documented marked clinical improvement at 72 hours and complete resolution of his corneal edema at two weeks.
Discussion
In the setting of ocular exposure to latex of Asclepias plants, the majority of cases document corneal endothelial toxicity without evidence of epithelial involvement.2,3,6 Despite this paradoxically nontoxic effect to the epithelium relative to the endothelium, varying degrees of endothelial toxicity have been demonstrated. This could potentially be explained by a dose effect; or perhaps some species are more toxic than others.
Fortunately, cellular disruption appears to be transient, which allows for restoration of the normal state of corneal dehydration. Interestingly, there has been a recorded case of toxicity caused by A. physocarpa (commonly known as “Balloon plant”). In this instance, more alterations in the corneal endothelium were noted, including sustained endothelial cell loss and the presence of polymegathism and pleomorphism on specular microscopy at follow-up visits.6 To our knowledge, this is the only reported case in which the patient was followed with specular microscopy. This case raises the possibility of permanent endothelial damage after exposure to these plants.
Despite the wide distribution of Asclepias, there is a relative paucity of examples of toxic exposure in the literature. Recognition of this clinical presentation through a complete clinical history is crucial for preventing misdiagnosis and providing appropriate management for patients. Possible exposure to the latex of milkweed plants should be included in the differential diagnosis for the presentation of sudden-onset corneal edema.
Finally, simple health measures for farmers, gardeners, and landscapers—such as handwashing, avoiding hand-to-eye contact, and using gloves while handling any type of milkweed—are key to preventing this kind of injury.
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*Patient’s name is fictitious.
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1 Moshirfar M et al. Ophthalmol Ther. 2019;8:195-213.
2 Chakraborty S et al. Arch Ophthalmol. 1995;113(8):974-975.
3 Amiran MD et al. Eye (Lond). 2011;25(7):961-963.
4 DelMonte DW, Kim T. J Cataract Refract Surg. 2011;37(3):588-598.
5 Hatou S et al. Curr Eye Res. 2009;34(5):347-354.
6 Pina S et al. Case Rep Ophthalmol Med. 2014;2014:829469.
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Dr. Carr is an ophthalmology resident at the Medical College of Georgia at Augusta University in Augusta, Ga. Dr. Young is an ophthalmology resident, and Dr. Rosa is Professor of Ophthalmology; both are at the Baylor Scott & White Health Medical Center in Temple, Texas. Financial interests: None.