Case report
A 40-year-old male patient with past medical history of chronic neck pain and stiffness presented to Southampton Eye Unit with sudden painless reduction of vision in his left eye (OS). At presentation, his visual acuity (VA) was 6/6 in the right eye (OD) and 6/60 Snellen OS.
Anterior Segment (AS) examination, intraocular pressure (IOP) and dilated fundoscopy of the right eye were all unremarkable. AS examination and IOP of the left eye were also unremarkable. However, dilated retinal examination of the left eye revealed mild vitreous haemorrhage, a large sub-hyaloid (pre-retinal haemorrhage) and multiple flame-shaped haemorrhages at the macular level (Fig. 1a).
The patient denied any past history of trauma. Past medical history was remarkable for chronic neck pain and stiffness, for which the patient used to take over-the-counter ibuprofen. From the patient’s drug history, it was revealed that the patient used to take Tolperisone (Mydocalm®) regularly, a centrally-acting muscle relaxant to help alleviate his chronic neck issue. He stopped ibuprofen before starting Tolperisone. He reported that he had been taking Tolperisone tablets 150 mg/day for the last month (he skipped some days) before presentation. One week before presentation, he stopped taking Tolperisone, as he had noticed a mild visual obscuration. One week later, he reported sudden painless central visual loss in the left eye. No other pertinent medical or family history was observed. Of note, he also reported no history of strenuous activities forcing him to breathe with a closed glottis.
Spectral domain-optical coherence tomography (SD-OCT) was carried out and confirmed the presence and the location of the bleed in the sub-hyaloid (pre-retinal) space with no changes at the level of the inner or outer retinal layers (Fig. 1b).
In the absence of past medical history of diabetes, hypertension or any other cardiovascular disease, we hypothesize that the bleed is likely to have been caused by the use and sudden cessation of tolperisone. Treatment options were discussed with the patient and both pars plana vitrectomy and observation were offered. The patient opted for a conservative approach.
One week later, BCVA OS was 6/36 and colour photographs and SD-OCT showed a partially organized clot in the sub-hyaloid space (Fig. 1c, d).
Six weeks later, the clot showed complete organization (Fig. 1e, f).
At 9 months post presentation, VA had improved to 6/6 in the affected eye with complete resolution of the pre-retinal bleed (Fig. 1g, h).
Discussion
Tolperisone (trade names include Biocalm®, Muscodol®, Mydeton®, Mydocalm®, Mydoflex®, Myolax®, Myoxan® and Viveo®) has been used in different rheumatological, orthopaedic, traumatic neurological disorders (e.g. cerebral palsy, traumatic brain injury, stroke, multiple sclerosis and different forms of spinal cord injury) [1].
Tolperisone is structurally related to the sodium channel antagonist local anaesthetics (lidocaine and procaine) and exhibits membrane stabilizing potency, which is characteristic of local aesthetic agents [1].
In addition, it increases blood flow to skeletal muscles [2]. The muscle relaxation caused by tolperisone is dose dependent [3].
In the case reported here, the patient was on no other medications and there was no other past medical or ocular history. We hypothesize that tolperisone may have caused the sub-hyaloid haemorrhage observed here.
To the best of our knowledge, this is the first case describing a sub-hyaloid haemorrhage secondary to tolperisone. This medication is not licensed for use in the United Kingdom. This potential side effect was also reported to the MHRA via their yellow card system.
Further research is needed to investigate the potential role of centrally acting muscle relaxants in inducing such an adverse reaction.
References
Tekes K1. Basic aspects of the pharmacodynamics of tolperisone, a widely applicable centrally acting muscle relaxant. Open Med Chem J. 2014;11:17–22.
Quasthoff S, Möckel C, Zieglgänsberger W, et al. Tolperisone: a typical representative of a class of centrally acting muscle relaxants with less sedative side effects. CNS Neurosci Ther. 2008;14:107–19.
Pratzel HG, Alken RG, Ramm S. Efficacy and tolerance of repeated oral doses of tolperisone hydrochloride in the treatment of painful reflex muscle spasm: results of a prospective placebo-controlled double-blind trial. Pain. 1996;67:417–25.
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Tsokolas, G., Almuhtaseb, H., Hanifudin, A. et al. Tolperisone, a centrally-acting muscle relaxant: a possible cause of macular haemorrhage. Eye 34, 1380–1381 (2020). https://doi.org/10.1038/s41433-019-0578-9
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DOI: https://doi.org/10.1038/s41433-019-0578-9
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