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 Table of Contents  
CASE REPORT
Year : 2021  |  Volume : 1  |  Issue : 2  |  Page : 240-241

Keratouveitis associated with herbal eye drop containing Butea monosperma, Achyranthes aspera and Boerhavia diffusa extracts


Department of Ophthalmology, Swami Rama Himalayan University, Dehradun, Uttarakhand, India

Date of Submission11-Mar-2020
Date of Acceptance07-Sep-2020
Date of Web Publication01-Apr-2021

Correspondence Address:
Dr. Manish Jain
Department of Ophthalmology, Swami Rama Himalayan University, Dehradun - 248 016, Uttarakhand
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijo.IJO_517_20

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  Abstract 


Herbal medicine Isotine eye drop contains extract from Butea monosperma, Achyranthes aspera, Boerhavia diffusa and elements such as aluminum, boron, copper, and zinc. Multiple indications are claimed and the only reported side effects are ocular irritation and foreign body sensation. Herein, a case of keratouveitis with glaucoma and pupillary abnormality is reported following its uniocular use for three days. Toxic and immunomodulatory properties of the ingredients are discussed.

Keywords: Achyranthes aspera, Boerhavia diffusa, Butea monosperma, glaucoma, keratouveitis


How to cite this article:
Jain M. Keratouveitis associated with herbal eye drop containing Butea monosperma, Achyranthes aspera and Boerhavia diffusa extracts. Indian J Ophthalmol Case Rep 2021;1:240-1

How to cite this URL:
Jain M. Keratouveitis associated with herbal eye drop containing Butea monosperma, Achyranthes aspera and Boerhavia diffusa extracts. Indian J Ophthalmol Case Rep [serial online] 2021 [cited 2021 Apr 20];1:240-1. Available from: https://www.ijoreports.in/text.asp?2021/1/2/240/312415



Adverse drug events are generally under reported. Herbal medications have an instant appeal as nature's own therapies that are free of adverse effects. This myth creates a window of opportunity for charlatans who come up with hyperboles. A case of keratouveitis with glaucoma following use of a herbal medication containing extract from Butea monosperma, Achyranthes aspera, Boerhavia diffusa and elements such as aluminum, boron, copper and zinc is presented.


  Case Report Top


A 19-year-old pharmacy student presented with unilateral progressive blurring and redness following use of a herbal eye drop in the right eye. She had no contributory systemic and family history except for bilateral asthenopia and computer vision syndrome during her ongoing examinations. As she ran out of her supply of lubricants, she used an over the counter herbal medication “Isotine eye drop” based on the recommendation of a hostel mate. Intense irritation in her right eye deterred her from using it in left eye. Her irritation worsened the next morning. Going by the. range of indications of the eye drop, she decided to continue it in her right eye. With further worsening, she presented on third day. Her unaided visual acuity was 20/60; N8, correctable to 20/30; N8 (OD) and 20/20; N6 (OS). She had diffuse congestion, superficial punctuate keratitis [Figure 1]a in the lower half of right cornea, mild corneal edema, mid dilated nonresponsive pupil and aqueous flare. Corneal sensation was normal in both eyes. The left eye was normal. Intraocular pressure was 33 and 18 mm Hg in right and left eyes. There was no vitritis; the disc, macula, and retinal periphery appeared normal. No other medications were used by her. Her condition was described as keratouveitis with secondary glaucoma.
Figure 1: (a): Day 3 post medication, showing punctate staining mostly in the lower half of cornea. (b): Day 12 post medication, showing large keratic precipitates, dilated pupil; synechia was present from 2 O' clock to 4 O' clock position

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She was asked to discontinue the drops and prescribed Tab acetazolamide twice a day along with prednisolone 1% eye drop 2 hourly and a combination of timolol 0.5% with brimonidine 0.15%, twice a day. Next day her intraocular pressure was 22 mm Hg. Ocular congestion and corneal edema had reduced and vision improved to 20/20; N8 in right eye. On day 12, she had keratic precipitates [Figure 1]b, immobile pupil and a synechia that could not be broken with homatropine; subsequent attempt to constrict the pupil with pilocarpine eye drop were also futile. Anisocoria and reduced near vision in the affected eye persisted when last seen two months after the episode.


  Discussion Top


Isotine eye drop is promoted as an ayurvedic panacea for multiple ocular ailments.[1] These include immature cataract, hypermetropia, myopia, amblyopia, night blindness, retinitis pigmentosa, color blindness, glaucoma, diabetic retinopathy, solar retinitis, photokeratitis, macular degeneration, optic nerve degeneration, side effects of excessive use of steroids and antibiotics, post-cataract extraction status, sudden visual loss due to trauma or following cataract operation/LASIK/retinal detachment surgery and snake bite, eye stress and computer vision syndrome. The product information mentions that a similar drug Netra Sudharak Ark (Palashanjan) containing Butea monosperma is mentioned in classical ayurvedic literature to be effective in cataract, night blindness, conjunctivitis and has removed spectacles of thousands of patients.[1] Ingredients of Isotine include Palash (Butea monosperma 0.3%), Apamarga (Achyranthes aspera 0.3%), Punarnava (Boerhavia diffusa 0.3%), zinc oxide 0.06%, Suhaga (Calcined Borax 2%), alum 0.4%, Mentha piperita 0.04%, tuth bhasma (Copper sulphate 0.04%) and bezalkonium chloride 0.01%. The only reported side effects are irritation and foreign body sensation as noticed by this patient. Her previous history and medical records did not reflect any existing major illness or uveitis. The author contacted her hostel mate over phone who corroborated the chain of events, ruling out the possibility of malingering or other self inflicted injury. Further, the classical features of viral keratouveitis, such as stromal keratitis, fine keratic precipitates, and reduced corneal sensation were absent in this case.[2] Temporal sequence supported the association with the medication. Her first reported symptom was intense irritation corresponding to punctuate keratitis. Typically ocular allergies and drug-induced corneal epithelial toxicity affect the exposed and inferior part. Copper sulfate is a known ocular irritant that induces conjunctivitis and corneal clouding.[3] In vitro studies have shown evidence of cytotoxicity, oxidative stress, and production of proinflmmatory cytokine, interleukin-8 with zinc.[4] As the uveitis evolved, she had keratic precipitates by day twelve. It is likely that the initial irritation was due to inorganic elements. The pH of the concoction was found to be 6; though not unusual for some eye drops, it is far from the pH (7.4) of normal tears.[5] Ocular surface damage induced by this acidic pH may have facilitated the penetration of active phytochemicals. Subsequent penetration of other active herbal ingredients possibly contributed to the onset of uveitis, while accompanying inflammation caused secondary glaucoma. The synechia observed on day twelve did not look like a classical broad posterior synechia of a granulomatous inflammation; instead, it represented an opportunistic adhesion secondary to a pupil refractory to both bright light and accommodation. Interestingly, Achyranthes aspera has known neurotoxic and cardiotoxic effects.[6],[7] Of these, the neurotoxic effects were mediated through GABAergic pathways, while the cardiac effects needed dopamine for reversal of life-threatening hypotension.

Herbal ingredients from all three plants have varied immunomodulatory properties: drop in pro-inflammatory cytokines, increased apoptosis and humoral response.[8],[9],[10],[11],[12] Butea monosperma extract decreases cytokines such as interleukins (IL 1 Beta, IL 8) in vitro, while Punarnavine extracted from Boerhavia diffusa-reduced tumor necrosis factor and interleukins (TNF-alpha, IL-1beta, and IL-6). Modulation of humoral response following intraperitoneal injection of Achyranthes aspera extract suggests its adjuvant potential.

No studies are available on direct effects on cytokine profile in vivo following ocular administration. Concurrent epithelial toxicity presumably induced by inorganic components renders the possibility of an intrinsic uveitis unlikely; further, the observed effects continued despite administration of topical steroids eventually culminating in pupillary abnormality. Theoretically, a drop in pro-inflammatory activity would prevent ocular inflammation. However, increased pro-apoptotic effects could provide an alternative explanation of observed pupillomotor damage besides chemical toxicity. For ethical reasons, it was not feasible to re-challenge her.


  Conclusion Top


This is the first case report of keratouveitis associated with a herbal medication. It was reported to the state pharmaco-vigilance authorities for appropriate actions.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Available from: https://www.ayurtimes.com/isotine-eye-drop/.  Back to cited text no. 1
    
2.
Agrawal RV, Murthy S, Sangwan V, Biswas J. Current approach in diagnosis and management of anterior uveitis. Indian J Ophthalmol 2010;58:11-9.  Back to cited text no. 2
[PUBMED]  [Full text]  
3.
Clayton GD, Clayton FE, editors. Patty's Industrial Hygiene and Toxicology. 3rd ed. Vol 2, Part 6, toxicology. NY; 1981.  Back to cited text no. 3
    
4.
Heng BC, Joachim SL. Toxicity of zinc oxide (ZnO) nanoparticles on human bronchial epithelial cells (BEAS-2B) is accentuated by oxidative stress. Food Chem Toxicol 2010;:1762-6.  Back to cited text no. 4
    
5.
Lim LT, Ah-Kee EY, Collins CE. Common eye drops and their implications for pH measurements in the management of chemical eye injuries. Int J Ophthalmol 2014;7:1067-8.  Back to cited text no. 5
    
6.
Gawande DY, Druzhilovsky D, Gupta RC, Poroikov V, Goel RK. Anticonvulsant activity and acute neurotoxic profile of Achyranthes aspera Linn. J Ethnopharmacol 2017;202:97-102.  Back to cited text no. 6
    
7.
Han ST, Un CC. Cardiac toxicity caused by Achyranthes aspera. Vet Hum Toxicol 2003;45:212-3.  Back to cited text no. 7
    
8.
Krolikiewicz-Renimel I, Michel T, Destandau E, Reddy M, André P, Elfakir C, et al. Protective effect of a Butea monosperma (Lam.) Taub flowers extract against skin inflammation: Antioxidant, anti-inflammatory and matrix metalloproteinases inhibitory activities. J Ethnopharmacol 2013;148537-43.  Back to cited text no. 8
    
9.
Choedon T, Shukla SK, Kumar V. Chemopreventive and anti-cancer properties of the aqueous extract of flowers of Butea monosperma. J Ehnopharmacol 2010;129:208-13.  Back to cited text no. 9
    
10.
Rao YV, Duddukury GR, Gosipatala SB, Athota RR. Immunomodulatory activity of achyranthes aspera on the elicitation of antigen-specific murine antibody response. Pharmaceutical Biology 2001;40:175-8.  Back to cited text no. 10
    
11.
Narayan C, Kumar A. Antineoplastic and immunomodulatory effect of polyphenolic components of Achyranthes aspera (PCA) extract on urethane induced lung cancer in vivo. Mol Biol Rep 2014;41:17-191.  Back to cited text no. 11
    
12.
Manu KA, Kuttan G. Immunomodulatory activities of Punarnavine, an alkaloid from Boerhaavia diffusa. Immunopharmacol Immunotoxicol 2009;31:377-87.  Back to cited text no. 12
    


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