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CASE REPORT
Year : 2019  |  Volume : 67  |  Issue : 10  |  Page : 1768-1771

Reversible blindness in a patient with closantel toxicity


1 Department of Vitreo Retina, Aravind Eye Hospital, Madurai, Tamil Nadu, India
2 Department of Paediatric Ophthalmology, Aravind Eye Hospital, Madurai, Tamil Nadu, India

Date of Submission16-Dec-2018
Date of Acceptance02-Jun-2019
Date of Web Publication23-Sep-2019

Correspondence Address:
Dr. Chitaranjan Mishra
Department of Vitreo-Retina, Aravind Eye Hospital, Anna Nagar, Madurai - 625 020, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijo.IJO_2070_18

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  Abstract 


To describe the optical coherence tomography (OCT) and electrophysiological changes in a case of closantel toxicity. A 25-year-old patient presented with sudden painless defective vision following intake of closantel. Visual acuity (VA) was counting fingers at 5 m in both eyes (BE). OCT revealed disruption of outer retinal layers and electroretinogram (ERG) and visual evoked potential (VEP) were subnormal in BE. The patient was treated with systemic corticosteroids, after which his VA improved to 6/9, OCT revealed preservation of central outer retinal layers, and ERG and VEP responses improved in BE. This is the first case report of successful treatment with systemic steroids for closantel-related reversible blindness.

Keywords: Closantel, reversible blindness, side effect, toxicity


How to cite this article:
Kumar K, Mishra C, Anjanamurthy R, Kannan NB, Ramasamy K. Reversible blindness in a patient with closantel toxicity. Indian J Ophthalmol 2019;67:1768-71

How to cite this URL:
Kumar K, Mishra C, Anjanamurthy R, Kannan NB, Ramasamy K. Reversible blindness in a patient with closantel toxicity. Indian J Ophthalmol [serial online] 2019 [cited 2024 Mar 29];67:1768-71. Available from: https://journals.lww.com/ijo/pages/default.aspx/text.asp?2019/67/10/1768/267421



Closantel is a halogenated salicylanilide used for the management of parasitic infestation in animals and is contraindicated in humans.[1] Overdose of closantel has been reported to be neurotoxic, ophthalmotoxic, and hepatotoxic in animals. Closantel toxicity is having no specific antidote and the reports in humans are limited.[2] In this study, we describe the reversible blindness and document optical coherence tomography (OCT) and electrophysiological findings in a patient of accidental ingestion of closantel.


  Case Report Top


A 25-year-old farmer presented with sudden painless defective vision in BE for 3 days. He did not give any other systemic illness and his systemic examination including central nervous system and per-abdominal examination was normal. He had ingested closantel oral solution (Clositel, manufactured by Ratnamani Healthcare PVT., Ltd., Gujarat, India, meant for treatment of parasitic infestation of cattle and sheep), mistaking it for cough syrup. The ingested dose of closantel was 2250 mg (15 ml, each ml containing 150 mg). His visual acuity (VA) was counting fingers at 5 m in BE. There was no relative afferent pupillary defect, ocular movements were full, and rest anterior segments were normal. Visual fields were not recordable in BE. Intraocular pressure of both the eyes was 16 mm Hg. Fundus examination showed mild temporal optic disc pallor [Figure 1]a and [Figure 1]b and FFA showed stippled hyperfluorescence [Figure 1]c and [Figure 1]d in BE. Fundus autofluorescence of BE showed normal macula in both the eyes [Figure 1]e and [Figure 1]f. OCT of macula of BE revealed gross disruption of outer retinal layers, namely external limiting membrane, myoid zone, ellipsoid zone, outer segment of photoreceptors, interdigitation zone, and retinal pigment epithelium [Figure 2]a and [Figure 2]b. Electrophysiological tests were done according to standard protocols recommended by the International Society for Clinical Electrophysiology of Vision.[3],[4] ERG of BE showed severe decrease in both rod and cone responses [[Figure 3] Panel a]. Flash VEP was not recordable. Pattern VEP showed decreased amplitude in BE and delayed P100 latency in the right eye (RE), suggestive of optic nerve dysfunction in RE [[Figure 4] Panel a]. The patient was treated with intravenous injection of methyl prednisolone 1 g (once) daily for 3 days followed by oral prednisolone 40 mg (once daily and tapered. At one month follow-up, his VA improved to 6/9 in BE. OCT revealed preservation of central outer retinal layers with parafoveal loss of IS-OS junction [Figure 2]c and [Figure 2]d. Visual fields of BE were normal. ERG showed improved responses of mixed rod cone, cone responses, oscillatory potentials, and increased amplitude and decreased latency in 30-Hz flicker waves, suggestive of improved rod and cone responses in BE [[Figure 3] Panel c]. Flash VEP showed improved responses, and there was no change in pattern VEP [[Figure 4] Panel c]. Normal ERG [[Figure 3] Panel b] and Normal VEP [[Figure 4] Panel b] are given for reference.
Figure 1: (a and b) Fundus photo—showing temporal optic disc pallor in both eyes (BE). (c and d) fundus fluorescein angiography—showing stippled hyperfluorescence in BE. (e and f) Fundus autofluorescence of macula—normal in BE

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Figure 2: (a and b) Pretreatment OCT showing loss of outer retinal layers (arrow marks). (c and d) Posttreatment OCT showing presence of subfoveal outer retinal layers (arrow marks) and loss of parafoveal outer retinal layers (star marks)

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Figure 3: Upper panels are dark-adapted 10 ERG (strong flash ERG) and lower panels are light-adapted 30 Hz flicker ERG. (a) Pretreatment ERG showing depressed rod and cone response. (b) Normal ERG of a subject for reference. (c) Posttreatment ERG showing improved rod and cone response

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Figure 4: Upper panels—BE, middle panels—RE, lower panels—left eye (LE). (a) Pretreatment VEP. Flash VEP was not recordable. Pattern VEP showed decreased amplitude in BE and delayed P100 latency in the RE. (b) Representative normal VEP (flash and pattern) of a subject for reference. (c) Posttreatment (1 month) VEP. Flash VEP showed improved responses, and there was no changes in pattern VEP

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  Discussion Top


Closantel is prescribed for the treatment and control of both nematodes and liver fluke infestations in sheep and cattle and is effective against Haemonchus contortus, Fasciola hepatica, and Oestrus ovis larvae.[5] Closantel acts via energy metabolism pathway by uncoupling oxidative phosphorylation in liver flukes.[1] Following oral intake in animals, the peak plasma concentration reaches in 8–48 h with elimination half-life of 2 to 3 weeks. Closantel is poorly metabolized and its tissue distribution is limited (distribution volume <0.15 L/kg) by its strong protein binding (>99.9% to plasma albumin).[6] Its pharmacokinetics in humans are unknown.[2]

In closantel toxicity, the pathological lesions described in animals include narrowing of intracanalicular optic nerve and optic disc atrophy.[1],[5] The histopathologic changes include severe myelinic edema, vacuolation,  Wallerian degeneration More Details, reactive astrocytosis and spongiform degeneration in the brain, and photoreceptor layer loss, and outer and inner nuclear layer damage in retina.[5]

Till date five publications (17 cases in total) of closantel toxicity in humans have been reported in English literature, out of which only one case, i.e. the one reported by Koziolek et al.[2] was successfully treated (by plasmapheresis) and had good visual outcome.[1],[2],[7],[8],[9] An outbreak of closantel toxicity was first described in Lithuania in 1993, where 11 women were wrongly prescribed closantel mistaking it to be a gynecological drug.[7]

In the current case, the pretreatment OCT scan of macula of BE was suggestive of severe disruption of photoreceptor layers and outer and inner nuclear layers. The ERG was suggestive of decreased response of the rods and the cones in BE. The VEP was suggestive of decreased amplitude and delayed latency in the RE. The exact mechanism of better visual outcome after treatment with systemic steroids was not well understood. However, with the knowledge that the peak plasma concentration in animals is described to be 8–48 h and presumably some inflammatory mediators result in toxic damage caused by closantel, the proposed explanation may be the early initiation of steroid treatment (on third day) resulted in limited exposure to the inflammatory and toxic effects of the drug. In all other case reports, the treatment was started much later. Tabatabaei et al.[1] has also described treatment with systemic steroids similar to the regimen in the current case. However, the poor outcome in their case may be ascribed to the late presentation of the patient (10 days). The dose consumed in the current case is 2250 mg, which is larger than the cases reported previously (1500 mg in the case reported by Tabatabaei et al.[1] and 1800 mg in the case reported byKoziolek et al.[2]), thus ruling out the possibility of smaller dose of the drug being the reason for better visual outcome. The documentation of preservation of subfoveal IS-OS junction in OCT and improved ERG and VEP responses support the posttreatment better visual outcome. Flash VEP showed improved responses, and there was no changes in pattern VEP. This could probably suggest that the cones are first to improve and long term follow-up is needed to document for the improvement of the rods. Probably closantel affected the phosphorylation of rhodopsin during phototransduction in outer segment of photoreceptors. We do acknowledge that multifocal ERG would have been a better modality to document the visual outcome.

This is the first case report of successful treatment with systemic steroids for closantel-related reversible blindness, which is known to have poor visual outcomes. Public health awareness about the toxicity of the drug is warranted. Prompt treatment with systemic steroids may be beneficial in cases presenting early.

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.
Tabatabaei SA, Soleimani M, Mansouri MR, Mirshahi A, Inanlou B, Abrishami M, et al. Closantel: A veterinary drug with potential severe morbidity in humans. BMC Ophthalmol 2016;16:207.  Back to cited text no. 1
    
2.
Koziolek MJ, Patschan D, Desel H, Wallbach M, Callizo J. Closantel poisoning treated with plasma exchange. JAMA Ophthalmol 2015;133:718-20.  Back to cited text no. 2
    
3.
McCulloch DL, Marmor MF, Brigell MG, Hamilton R, Holder GE, Tzekov R, et al. ISCEV standard for full-field clinical electroretinography (2015 update). Doc Ophthalmol 2015;130:1-12.  Back to cited text no. 3
    
4.
Odom JV, Bach M, Brigell M, Holder GE, McCulloch DL, Mizota A, et al. ISCEV standard for clinical visual evoked potentials: (2016 update). Doc Ophthalmol 2016;133:1-9.  Back to cited text no. 4
    
5.
Gill PA, Cook RW, Boulton JG, Kelly WR, Vanselow B, Reddacliff LA. Optic neuropathy and retinopathy in closantel toxicosis of sheep and goats. Aust Vet J 1999;77:259-61.  Back to cited text no. 5
    
6.
Michiels M, Meuldermans W, Heykants J. The metabolism and fate of closantel (Flukiver) in sheep and cattle. Drug Metab Rev 1987;18:235-51.  Back to cited text no. 6
    
7.
t Hoen E, Hodgkin C. Harmful human use of donated veterinary drug. Lancet 1993;342:308-9.  Back to cited text no. 7
    
8.
Essabar L, Meskini T, Ettair S, Erreimi N, Mouane N. Harmful use of veterinary drugs: Blindness following closantel poisoning in a 5-year-old girl. Asia Pac J Med Toxicol 2014;3:173-5.  Back to cited text no. 8
    
9.
Badrane N, Abbada A, Chaoui H, Aoued L, Rhalem N, Benjelloun BS, et al. Blindness following closantel poisoning: Report of three cases. XXXIII International Congress of the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) 28–31 May 2013, Copenhagen, Denmark. Clin Toxicol (Phila) 2013;51:280.  Back to cited text no. 9
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]


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