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Severe Systemic Toxicity Caused by Brimonidine Drops in an Infant With

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Severe Systemic Toxicity Caused by Brimonidine Drops in an Infant With Sir, At 3 weeks after presentation patching was Severe systemic toxicity caused by brimonidine drops commenced. There was a rebleed at 6 weeks. The steroid in an infant with presumed juvenile xanthogranuloma drops were increased to g. betamethasone 2-hourly and Systemic absorption of ophthalmic medications is known g. atropine 0.5% b.d., g. timolol 0.25%, g. dorzolamide 2% b.d. and acetazolamide 25 mg b.d. were continued. An to occur and can lead to toxicity. Infants especially are 1 examination under anaesthetic at 7 weeks showed the highly vulnerable to eye drop toxicity. We report the acute haemorrhage to have cleared although the iris was medical management of an infant, presenting with tented up to the cornea and an inferior iris mass was spontaneous hyphaema and raised intraocular pressure visible (Fig. 1). The corneal diameter was 12 mm, the lOP (lOP) due to presumed juvenile xanthogranuloma, was 10 mmHg and there was the start of an anterior leading to severe systemic toxicity caused by capsular cataract. brimonidine drops. The family failed to attend clinic on a number of occasions. At 6 months after presentation the lOP was Case report controlled and the medications were gradually An 8-week-old girl presented as an emergency with a discontinued, the lOP remaining stable. A sedated 10 day history of a red right eye. The parents had noted examination at 10 months after presentation showed the the right eye appeared both darker and larger than the lOP to be 17 mmHg, the corneal diameter 12 mm and the left and a white mark had developed at the bottom of the iris to have come away from the cornea, the iris mass iris. The infant was born at 41 weeks gestation via a having shrunk. caesarian section for fetal distress. She was a face Currently the infant can follow targets with the right presentation and developed a bruise on the forehead. eye and is tolerating patching poorly. The lOP is stable The parents were unemployed and lived in a hostel. without treatment and there is an anterior lens opacity. Examination revealed a distressed baby. The right cornea was cloudy with a diameter of 11.5 mm. There Comment was a hyphaema of half to three-quarters of the anterior All eye drops and systemic treatments have the potential chamber and the intraocular pressure (lOP) was to cause side-effects, especially in infants. Beta-blocker 44 mmHg (Perkins). There was a dull red reflex with no drops, atropine drops and carbonic anhydrase inhibitors fundal details visible. The left eye was normal. can all have significant systemic side-effects, some The infant was admitted for further investigation and 1 potentially fatal, including drowsiness. Infants, because treatment. The paediatrician found no other evidence of of their size and immature drug clearance, are highly non-accidental injury and no skin lesions. A full blood vulnerable to eye drop toxicity. Our patient had severe count and clotting screen were normal. Ultrasound of the floppy episodes in which extensive examination and eye and a CT scan of the orbit and brain found no investigations, including an infection screen (including a intraocular lesions or calcification, although the right eye lumbar puncture), metabolic screen, toxicological was larger than the left. Our working diagnosis was that investigations (looking for illicit drug administration), of juvenile xanthogranuloma. EEG and head CT scan by the paediatricians found no The treatment started was g. atropine 0.5% b.d., g. cause. The focus of attention was then on the infant's levobunolol 0.5% b.d., g. betamethasone 3-hourly and ophthalmic medication and, by a process of elimination, acetazolamide syrup 25 mg b.d. At 3 days the lOP was brimonidine drops were found to be the cause of these still elevated at 45 mmHg and at this stage g. floppy episodes. dorzolamide 2% b.d. and g. brimonidine 0.2% b.d. were Brimonidine tartrate is a highly selective added. At 8 days the lOP was 20 mmHg. cx2-adrenergic receptor agonist indicated for the chronic At 2 weeks after presentation the infant was admitted treatment of glaucoma and ocular hypertension in as an emergency under the paediatricians with a history of severe floppy episodes and failure to thrive. The baby became unrousable and hypotonic for several hours at a time. Thorough examination and extensive investigations, including an infection screen, metabolic screen, toxicology, EEG and a head CT scan found no cause. At this point it was thought that symptoms could be due to some of the topical or systemic medication the infant was on for her ocular condition. The f3-blocker, atropine and acetazolamide were discontinued with no improvement in her systemic condition. The brimonidine drops were then stopped with an immediate cessation in the infant's floppy episodes. After this the other medications were cautiously Fig. 1. Photograph of the right eye showing the iris tented up to the re-introduced and there were no further systemic cornea, an inferior iris mass and a streak of organised blood in the problems. anterior chamber. 797 adults? Brimonidine lowers lOP through a dual 5. Karcioglu ZA, Mullaney PB. Diagnosis and management of iris juvenile xanthogranuloma. J Pediatr Ophthalmol mechanism of action: it reduces aqueous humour 3 Strabismus 1997;34:44-51. production and increases uveoscleral outflow. 6. Casteels I, Olver J, Malone M, et al. Early treatment of juvenile Significant systemic absorption of brimonidine eye drops xanthogranuloma of the iris with subconjunctival steroids. occurs in adults, peak plasma concentrations occurring Br J Ophthalmol 1993;77:57--60. within 1-4 h with a half-life of approximately 2.5 h? 7. Hadden OB. Bilateral juvenile xanthogranuloma of the iris. Br J Ophthalmol 1975;59:699-702. Systemic metabolism of brimonidine is primarily by the 8. MacLeod PM. Case report: juvenile xanthogranuloma of the liver and urinary excretion is the major route of iris managed with superficial radiotherapy. Clin Radiol ? elimination of the drug and its metabolites 1986;37:295--6. Brimonidine, like most drugs, has not been formally tested on children but has, along with other side-effects, G. Walters 4 Bradford Royal Infirmary caused drowsiness in adults. There have been several Bradford, UK unpublished reports of floppy episodes (J.A. Bradbury, Bradford Royal Infirmary, personal communication) and R.H. Taylor severe life-threatening reactions to brimonidine drops in York District Hospital York, UK infants (Allergan, USA, personal communication). The marked sensitivity of infants to brimonidine may be G. Walters � due to their size, immature metabolism and excretion of Bradford Royal Infirmary drugs or an increased receptor sensitivity. To our Duckworth Lane Bradford BD9 6RJ knowledge this is the first published report of a severe West Yorkshire, UK adverse reaction to brimonidine in an infant. This infant presented with spontaneous hyphaema and raised lOP. The most common cause for hyphaema s Sir, in any age group is trauma. Non-accidental injury should be excluded in any infant presenting in this way. Hormone replacement therapy and retinal vein The most frequently presenting sign in iris juvenile occlusion xanthogranuloma is hyphaema, although other causes The use of sex hormone preparations is a risk factor for 1 3 s cardiovascular and cerebrovascular disease. - A number should be sought. Once the diagnosis of iris juvenile of isolated case reports and a recent hospital-based xanthogranuloma is established treatment should be retrospective study of retinal vein occlusions have initiated rapidly. Several modes of treatment have been S implicated the oral contraceptive pill (OCP) but not advocated including topical steroids, subconjunctival 6 7 s hormone replacement therapy (HRT) as an independent steroids, systemic steroids and radiotherapy. Not all 4 risk factor for retinal vein occlusion. However, as an cases resolve with local or systemic steroids and increasingly large proportion of the population are using treatment should be adjusted according to clinical s HRT, reporting cases of retinal vein occlusion in patients status. If hyphaema and raised lOP is present, as in our 4 on this therapy may have management implications. We case, aggressive antiglaucoma medication with eye drops report a case of central retinal vein occlusion in a patient and oral acetazolamide, if necessary, should be s on HRT. instituted. In summary, this infant's eye with presumed juvenile xanthogranuloma was controlled medically with topical Case report steroids and with topical and systemic anti-glaucoma A 43-year-old woman presented with a 3 day history of medication. However, the child has been left with dense reduced visual acuity. There was no previous ophthalmic amblyopia and a lens opacity. This case illustrates the history. This patient had started HRT comprised of low­ potential pitfalls in prescribing adult drops, especially dose oestrogen and progesterone 5 weeks prior to some of the newer anti-glaucoma medications, in infants presentation to alleviate menopausal symptoms. Of note and we would recommend that great care be taken when was that she smoked 20 cigarettes a day, but there was no using these drops in infants and children. other significant medical or family history. On examination visual acuity was 1/60 in the right eye and 6/18 in the left. There was no relative afferent References pupillary defect and intraocular pressures were normal. 1. Mauger TF, Elson CL, editors. Ocular pharmacology. 6th ed. Fundal examination demonstrated in the right eye a St Louis: Mosby, 1994: 89,144-5, 177-8. 2. Cantor LB, Burke J. Drug evaluation: brimonidine. Expert swollen optic disc, tortuous retinal vessels and multiple Opin Invest Drugs 1997;6:1063-83. intraretinal haemorrhages consistent with a diagnosis of 3. Toris CB, Gleason ML, Camras CB, et al. Effects of central retinal vein occlusion.
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