British Journal of Ophthalmology 1996;80:823-826

Euphorbia sap keratopathy: four cases and a

possible pathogenic mechanism

Ingrid U Scott, Carol L Karp

AbstractAims-To report four cases of Euphorbiasap causing anterior segment toxicity.Methods-Medical records of four pa-tients who presented with Euphorbia sapkeratoconjunctivitis were reviewed. Clini-cal findings were compared with previ-ously published reports.Results-All ofthese patients experienceda similar clinical course. Initial contact withEuphorbia sap caused punctate epithelio-pathy; patients noted immediate burningand photophobia, but no visual loss. In allcases, patients experienced epithelialslough with delayed healing, requiringapproximately 9 days to heal the epithelialdefect. Patients were treated with topicalantibiotics, pressure patching, or a band-age contact lens, and final visual acuitieswere excellent in all cases. A review of theliterature revealed that Euphorbia sapcontains a diterpenoid diester which ex-hibits antineoplastic activity in rodents.Conclusions-Individuals who work withEuphorbia plants should be cautioned towear eye protection. Patients with Eu-phorbia sap anterior segment toxicityshould be informed that their conditionmay worsen initially, but that visualoutcome is generally excellent. The pro-gressive corneal epithelial sloughing anddelayed corneal epithelial healing may besecondary to the antineoplastic effects ofEuphorbia sap.(Br_' Ophthalmol 1996;80:823-826)

Bascom Palmer EyeInstitute, Departmentof Ophthalmology,University ofMiamiSchool ofMedicine,Miami, Florida, USAI U ScottC L Karp

Correspondence to: Carol LKarp, MD, Bascom PalmerEye Institute, 900 NW 17thStreet, Miami, FL 33139,USA.

Accepted for publication24 May 1996

Species of the plant genus Euphorbia are com-

monly employed as ornamental plants. Theseplants characteristically produce a milky sapwhich has been used to treat cancers, tumours,and warts from at least the time of Hippocra-tes.' Keratoconjunctivitis has been reported tooccur secondary to exposure to the sap of sev-

eral Euphorbia species, including tirucalli,"helioscopia,4 peplus,3 cyparissias,4 royleana,"lat_ris,'1"2 and lactea.' The pathogenesis ofEuphorbia sap keratoconjunctivitis, however, isunknown.We report four cases of Euphorbia sap

keratoconjunctivitis, including the first re-

ported case of keratoconjunctivitis secondaryto the sap of Euphorbia trigona, and compareour clinical findings with previously publishedreports.

MethodsThe medical records of all known patients whopresented to the Bascom Palmer Eye Institute

Figure 1 Euphorbia lactea sap drippingfrom the plantbelonging to the patient described in case 1.

or the W K Kellogg Eye Center withkeratoconjunctivitis secondary to plant sapbetween 1 January 1985 and 31 December1994 were reviewed. One patient presented tothe W K Kellogg Eye Center in Ann Arbor,Michigan, and three presented to the BascomPalmer Eye Institute in Miami, Florida. Clini-cal findings were compared with previouslypublished reports of plant sap keratoconjunc-tivitis. The genus and species of each plantwere determined by a horticulturist.

ResultsCASE 1A 38-year-old man was moving his plant(Euphorbia lactea), when he felt 'plant juice'splash into his right eye (Fig 1). The patientexperienced immediate burning and photo-phobia in his right eye. He noted no visionchanges. His symptoms persisted despite irri-gating his eye with water.Examination revealed a visual acuity of 6/6

in each eye. Slit-lamp examination revealedmild conjunctival injection, diffuse cornealpunctate epitheliopathy, and marked anteriorchamber flare in the right eye. The remainderof the examination of both eyes, including thefunduscopic examination, was unremarkable.The patient was treated with cyclopentolate

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Figure 2 Case 1.A 38-year-old man with cornealepithelial defect (arrows) and underlying stromal oedemasecondary to Euphorbia lactea sap toxicity.

1%, bacitracin ophthalmic ointment, and apressure patch. Examination of the right eye onthe following day revealed a visual acuity of6/18, moderate conjunctival injection andchemosis, a 3.0 x 5.5 mm area of comeal epi-thelial sloughing, and mild corneal oedema(Fig 2). The patient was treated with cyclopen-tolate 1% and bacitracin ophthalmic ointment.On day 3, the patient's visual acuity in the righteye was 6/60. The remainder of the examin-ation was unchanged. Treatment was contin-ued and the patient was followed daily. Hiscorneal epithelial defect required 9 days to healand the patient's examination returned to nor-mal, including a visual acuity of 6/6.

CASE 2A 59-year-old man was repotting his plant(Euphorbia trigona), when he felt sap from theplant splash into his eyes. He experienced theacute onset of burning, photophobia, and itch-ing in both eyes (Fig 3). He reported no changein his vision. His symptoms persisted despiteirrigating his eyes,with water.Examination 1 day after injury revealed a

visual acuity of 6/15 in the right eye and 6/12 inthe left eye. Slit-lamp examination revealedmoderate conjunctival injection and diffusecorneal punctate epitheliopathy bilaterally. Theremainder of the biomicroscopic examinationand the funduscopic examination of both eyeswere unremarkable. The patient was treatedwith artificial tears. Examination the followingday revealed a visual acuity of 6/21 in the righteye and 6/12 in the left eye. A 2.5 x 3.5 mmcorneal epithelial defect was present in theright eye (Fig 4); the punctate epitheliopathy inthe left eye had improved. The remainder ofthe examination was unchanged. The patientwas treated with a bandage contact lens andpolymyxin B sulphate-trimethoprim ophthal-mic drops in the right eye and followed daily.The patient wore a bandage contact lens for 2days and his corneal epithelial defect required9 days to heal. His visual acuity returned to 6/6in each eye.

CASE 3A 59-year-old woman was trimming her penciltree (Euphorbia tirucalli) (Fig 5) when she feltsap from the plant splash into her right eye. Shenoted immediate photophobia and foreignbody sensation in her right eye, but no visionchanges.

Figure 3 Euphorbia trigona belonging to the patientdescribed in case 2.

Figure 4 Case 2. A 59-year-old man with cornealepithelial defect (arrows) and necrotic epithelium (underleft arrow) secondary to Euphorbia trigona sap toxicity.

Figure S Euphorbia tirucalli belonging to the patientdescribed in case 3.

Examination revealed a visual acuity of 6/12in each eye. Slit-lamp examination revealedmarked conjunctival chemosis and mild diffusecorneal punctate epitheliopathy in each eye.The remainder of the examination of botheyes, including the funduscopic examination,was unremarkable. Examination of the righteye on the following day revealed a bestcorrected visual acuity of 3/60, marked con-junctival injection and chemosis, moderatecorneal oedema, and a 5.0 x 7.0 mm area ofcorneal epithelial sloughing (Fig 6). Thepatient was treated with a pressure patch for 3days, and prednisolone acetate 1% and hyos-cine (scopolamine) hydrobromide 0.25% for10 days. The corneal epithelial defect and cor-neal oedema required 10 days to resolve. Herbest corrected visual acuity returned to 6/6 ineach eye.

CASE 4A 44-year-old man was trimming his penciltree (Euphorbia tirucalli) when he felt sap fromthe tree 'spray' into his eyes. He noted the

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Euphorbia sap keratopathy

Figure 6 Case 3. A 59-year-old woman with cornealepithelial defect (arrows) secondary to Euphorbia tirucallisap toxicity.

acute onset ofburning and foreign body sensa-tion in both eyes, but experienced no change inhis vision. His symptoms persisted despite irri-gating his eyes with water.The patient presented to his local ophthal-

mologist, who further irrigated the patient'seyes and applied antibiotic drops and pressurepatches bilaterally. Because the patient noteddecreased visual acuity the following day, hepresented to the Bascom Palmer Eye Institute.Examination revealed a best corrected visualacuity of 2/60 in the right eye and 6/60 in theleft eye. Slit-lamp examination revealed mod-erate conjunctival injection and chemosis,diffuse corneal erosions, moderate cornealoedema, and mild anterior chamber cells andflare in each eye. There was a 5.0 x 4.0 mmcentral corneal epithelial defect in the right eyeand a 3.5 x 2.8 mm paracentral corneal epithe-lial defect in the left eye (Fig 7). The remainderof the examination was unremarkable. Thepatient was treated with pressure patches bilat-erally and was followed up by his localophthalmologist.

DiscussionThe Euphorbiaceae plant family includes ap-proximately 1500 species" and is named afterEuphorbus, the physician to King Juba II ofMauritania in AD 18.'4 Euphorbus discoveredthe therapeutic properties of Euphorbiaceaeplants growing in the Atlas mountains."4 In his1655 translation of the first century AD Greekherbal of Dioscorides, John Goodyear wrotethat Euphorbia sap 'takes away...hanging warts...[and] is good also for...pterygia and carbun-cles...gangrenes, fistulas'." In the early 19thcentury in England, it was reported thatEuphorbia sap 'removeth all blemishes of theskin'.'6 Euphorbia sap is used in India andAfrica to treat warts7 18 and in China to treatskin diseases.'9 Geran reported that Euphorbiasap extract showed significant antineoplasticactivity when tested in rodents against the sar-coma 180, Walker 256 carcinosarcoma, Lewislung carcinoma, and P-388 lymphocytic leu-kaemia.20 Kupchan et al isolated a diterpenoiddiester, ingenol 3,20-dibenzoate, as the majorantileukaemic component of sap from Euphor-bia esula extract."Although few cases ofEuphorbia sap anterior

segment toxicity have been reported, the litera-ture available does demonstrate similarities inthe mode of presentation and clinical course.

Figure 7 Case 4. A 44-year-old man with cornealepithelial defect in the left eye secondary to Euphorbiatirucalli sap toxicity. There is heaped up epithelium at themargins of the defect.

Euphorbia sap can lead to a spectrum ofanterior segment changes, including conjuncti-vitis, keratitis, and uveitis. In our patients, andnearly all reported cases, symptoms beganimmediately and worsened several hours todays after exposure. 237-1012 Further, in caseswhere an examination was performed on theday of injury and on the subsequent day, wors-ening vision and/or progressive epithelialsloughing were evident.2'7 This emphasises theimportance of frequent follow up for patientswith recent Euphorbia sap injuries. Patientsshould be warned that their symptoms mayworsen before improving. Cases treatedpromptly were left without visually significantresidua,"7 'o while patients with delayed treat-ment developed complications such as cornealulcers and corneal perforation, and were leftwith corneal scarring and decreased visualacuity."

All of our cases experienced a similar clinicalcourse. Initial contact with Euphorbia sapcaused a corneal punctate epitheliopathywhich progressed to larger corneal epithelialdefects requiring 9 or more days to heal despiteprompt treatment with pressure patching or abandage contact lens. This may be explainedby the antineoplastic effects of Euphorbia sap,which may hinder corneal epithelial replica-tion.

Patients who work with Euphorbia plantsshould be cautioned to wear eye protection.Patients with Euphorbia sap anterior segmenttoxicity should be informed that their condi-tion may worsen for several hours to days, butthat visual outcome is generally excellent.Ophthalmologists need to be aware of theimportance of following such patients closely,especially during the first several days, when amild corneal punctate epitheliopathy mayprogress to corneal slough.

The authors thank Mr Don Evans, Director of Horticulture atFairchild Tropical Garden, Miami, Florida, for his expertise inidentifying the genus and species of the plants described in thisreport.

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3 Crowder JI, Sexton RR. Keratoconjunctivitis resulting fromthe sap of candelebra cactus and the pencil tree. Arch Oph-thalmol 1964;72:476-84.

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