CET Ophthalmic drugs Part 3 — Mydriatic drugs – which ones to use when and how they work In the first of a two-part look at mydriatics, Dr Michael Johnson describes the indications for , what drugs to use and how they work. Module C19751, one specialist point for therapeutic optometrists, one general CET point for optometrists

he acts to improve argued that a dilated ocular examination (including surgery), and high or optical resolution, allows is an ideal that optometrists should a family history of non-trauma related for rapid control of offer all of their patients. However, . For comparison with retinal illumination, it is not customary to offer dilation population averages, the lifetime risk of and conveys emotion in routinely in primary eye care sight tests someone with more than six dioptres of non-verbal communication. within England and Wales owing to myopia developing a retinal detachment EnlargementT of the pupil is termed its associated inconvenience and low is about one in 20. It is my opinion that mydriasis and a reduction in the size of benefit-cost ratio for the majority of asymptomatic high myopes should be the pupil is termed . Physiological patients. A pragmatic compromise is that offered a dilated intraocular examination mydriasis occurs when the level of light patients with larger benefit-cost ratios bi-annually to detect retinal breaks that is dimmed, and in reaction to stress are identified and offered dilation. There could be treated before they lead to a and arousal. Miosis is a reaction to an is no definitive list of the patients that rhegmatogenous retinal detachment, increase in light. There are times when ‘must’ be dilated, and this is appropriate and this should be increased to annually an optometrist wants to override the given that individual circumstances for extreme myopes whose refraction physiological control of pupil size, and are by definition individual, and the exceeds 12 dioptres. Moreover, a dilated this article reviews why and how this opinions of clinicians along with the view of the anterior vitreous and fundus can be achieved. fashions of our profession differ with should be recommended in the strongest time and geography. What follows is a terms to anyone who has symptoms When to dilate guide to help optometrists make better suggestive of a retinal detachment The most common reason that an decisions (Table 1). or its precursor, a posterior vitreous optometrist chooses to dilate the pupil detachment. Symptoms of a posterior is to improve the view of the internal Risk of retinal detachment vitreous detachment include a sudden structures of the eye posterior to the . A retinal detachment is a relatively rare increase in the number of , often Therapeutic use of mydriatics invariably event, with an annual incidence of about with a large central opacity that moves makes use of chemically related one in 10,000 – lifetime risk about one with the eye, representing a Weiss ring, cycloplegic drugs, owing to their longer in 200.1 This risk is not shared evenly, and flashes. A retinal detachment may duration and the sometimes useful and some people are much more likely also be accompanied by a black shadow attribute of greater action on the ciliary to develop a detachment. The main risk that extends to the edge of vision. body. These medical indications include factors for retinal detachment are trauma lessening painful muscular spasm and Risk of macular disease breaking posterior synechiae in iritis, Table 1 It is difficult to confidently assess disrupting ciliovitreal block in aqueous the macula without dilation because misdirection (malignant) , Indications for dilated ocular examination its examination is associated with improving access to the posterior ● Risk of retinal detachment the strongest light-induced miosis. segment in surgery, and penalisation Flashes and floaters Furthermore, the most important sign in therapy for . Lattice degeneration macular disease is elevation or thickening, Viewing through an undilated pupil Recent blunt trauma which represents the accumulation of can be likened to peering through a High myopia fluid within or under the , and keyhole, with the situation compounded Family history of retinal detachment this demands stereoscopic viewing. In by the miosis triggered by the high light Post-intraocular surgery my opinion, a dilated examination of level associated with most examination ● Risk of macular disease the macula is indicated when there are techniques. It is certainly possible to New distortion complaints of new distortion, or reduced get a view through an undilated pupil AMD and reduced acuity acuity in persons with AMD or diabetic in most patients, at least with one eye, Numerous soft drusen , or at high risk of choroidal but dilation always gives a better view ● Specific conditions neovascularisation due to numerous soft by improving coverage, stereopsis and Diabetes (not screened) drusen or a history of wet AMD and clarity. In particular, without dilation not being monitored by the hospital eye it is not possible to optimally visualise Pigmented fundus lesion service. the peripheral retina, vitreous, or to Suspected glaucoma achieve stereoscopic appreciation of the Suspected papilloedema Specific conditions or macula (even when it can Penetrating trauma There are some specific conditions or easily be seen monocularly). It may be clinical scenarios that warrant dilation.

18 | Optician | 24.08.12 opticianonline.net Continuing education CET

nerve supply that originates from the leaves to dilate women’s to make Edinger Westphal nucleus and arrives them appear more amorous. Also, it has at the eye via the oculomotor nerve, been argued that the alkaloids produced ciliary ganglion and short ciliary nerves. by this genus of plants have evolved to The dilator muscle is composed of poison unwanted insects tempted to feast radial fibres, like spokes of a wheel, on their foliage in a manner analogous to that converge from the circumference chemical warfare. of the iris toward the centre and blend is an drug, with fibres of the sphincter muscle which means that it acts to frustrate near the pupil margin. It is controlled cholinergic nerves (those using by the sympathetic nervous system catecholamine such as acetycholine as with a nerve pathway that originates neurotransmitters) that form part of in the hypothalamus, loops down to the the parasympathetic nervous system. cervical portion of the spine and then The drug binds to cholinergic receptors travels upward towards the eye via the on the sphincter (and the ) carotid plexus, cavernous sinus and the where it shields them from acetycholine Figure 1 Iris muscles long ciliary nerves. and prevents it from triggering muscular Mydriatics can work on either end of contraction. In essence, anticholinergic Most diabetics have a retinal photograph the push-pull system controlling pupil drugs cover the ears of the iris sphincter taken annually, but in the rare instance size, namely by preventing contracture of so it cannot hear the nerves shouting. The that this is not being done then these the iris sphincter muscle, or augmenting effect is pupil dilation, and importantly, patients should be dilated. In patients the contraction of the iris dilator muscle. an abolition of the normal light reflex. with suspected uveitis dilation helps It should also be appreciated that the tone Atropine also causes pronounced better identify small numbers of cells or of the ciliary body is also controlled by cycloplegia. flare in the anterior chamber due to the cholinergic nerves, and so anticholinergic enhanced contrast with the black pupil, mydriatics have a spill-over of effect on and allows for better examination for . Indeed, mydriatic and The natural alkaloid atropine was used cells within the vitreous; furthermore, cycloplegic drugs that act on cholinergic for many years in , but dilation (and often cycloplegia) is used nerves differ in their strength, rather than clinicians, and especially patients, were therapeutically in these patients to in their pharmacological mechanism of inconvenienced by its long half-life lessen painful spasm of the iris and action. Cycloplegic drugs always cause that meant its dilation and cycloplegic break posterior synechiae. Dilation is pupil dilation in addition to their effect on effects persisted for many days, essential for good stereopsis, even when the ciliary body, whereas drugs marketed perhaps for as long as a week. This a good monocular view is possible, as mydriatics are less potent and so prompted the development of a short- and so is indicated when assessing have reduced effect on accommodative acting alternative, and the fruit of this possible elevation of pigmented fundal function. labour was a synthetic compound that lesions or borders of the optic nerve answered many of the practical failings when malignancy or papilloedema are Natural alkaloids of atropine. The synthetic derivative was suspected, and the cupping of the optic The first mydriatics were plants such as named tropicamide, which produces nerve when an such mandrake, which was used (and abused) dilation quicker and has a much shorter as glaucoma is suspected. Additionally, by many ancient civilisations, including duration. As an added benefit, it does although rare for optometrists in primary the Hebrews, Greeks and Romans. not cross the blood-brain barrier, and so care, any patient presenting with a recent This perennial herb is a narcotic and in contrast to atropine there is no risk history of high speed impact injury to the so serves to dull the perception of of central nervous system dysfunction eye, especially when working metal and pain through central mechanisms. In that can lead to amnesia, confusion in the presence of a corneal scar, requires ocular inflammation it also lessens pain and excitation. Tropicamide gives good dilation to more confidently exclude caused by iris spasm as a result of the dilation in about 20min, and this rapid a penetrating foreign body that can anticholinergic effect from its high action is the result of a relatively low PKa self-seal its entry wound. Indeed, owing alkaloid content. In addition to pain of 5.4 (versus 9.8 for atropine), which to the sometimes dire risk of the often relief, the Greeks and Romans made use means that its penetration across the lipid delayed consequences of not finding a of the dilating properties of mandrake membrane of the corneal epithelium is ferrous intraocular foreign body these to improve access to the cataractous enhanced by the low proportion of the patients usually go on to have an X-ray. in couching operations, and to simulate drug in ionised form at physiological pH Finally, many imaging technologies get the pupil signalling of sexual arousal in (about 2.3 per cent). Dilation begins to better pictures when the pupil is dilated, courtship and religious ceremonies. diminish after 2hrs and pupil size has and this is particularly the case in older The vogue of mydriatics in Greece and typically returned to its habitual level persons with senile miosis and . Rome was lost during the succeeding after 4-6hrs. The cycloplegic effect of centuries. It was only towards the end tropicamide is generally only noticed Mydriatic drugs of the 18th century that the mydriatic by early incipient presbyopes, especially effect of the herb belladonna, more those with uncorrected hypermetropia, Mechanisms of action commonly known as deadly nightshade and early presbyopes who have little The size of the pupil is governed by the due to its lethal effect as a poison, was accommodative reserve and incomplete interplay of the sphincter and dilator recognised by the medical establishment, near correction. muscles within the iris (Figure 1). The which subsequently led to the isolation Tropicamide is available in 0.5 per cent sphincter muscle is about 1mm wide of atropine. As an aside, the name and 1 per cent concentrations in both and runs circumferentially around the belladonna, meaning ‘beautiful lady’, preserved multiuse bottles and more pupil margin. It has a parasympathetic comes from the first use of the plant popularly as non-preserved single-use opticianonline.net 24.08.12 | Optician | 19 Continuing education CET

Figure 2 The quicker with , with dilated pupil size normal pupil size returning in 3-6hrs is similar for depending on the concentration used, 0.25 per cent, with the effects diminishing with time 0.5 per cent and due to its metabolism by the enzyme 1 per cent monoamine oxidase (MAO) following Tropicamide uptake into presynaptic nerve cells. – adapted from Experiments have demonstrated that Marchini et al, phenylephrine has no direct effect on 20032 accommodation, but some patients will experience reduced near function due to impaired visual feedback to the accommodative drive resulting from the degraded optical qualities of the eye when the pupil is dilated. Phenylephrine stings more than tropicamide, especially the stronger 10 per cent formulation, and may cause an epitheliopathy. Also, owing to a strong action on the dilator muscle, the 10 per cent formulation may cause individuals to develop transient Minims. The 0.5 per cent formulation is alpha-selectors with reduced affinity for pigment floaters in the anterior chamber already towards the top of the sigmoidal beta-receptors, and lasts longer because it that can be misinterpreted as anterior dose-response curve for this drug, and is not broken down by the extracellular uveitis or a microscopic . so doubling the strength only leads enzyme catechol-o-methyltransferase Phenylephrine eyedrops do not to a marginal increase in dilation, but (COMT) that operates within the only affect the iris. The drug is a is associated with the drawbacks of a synapse. vasoconstrictor and so causes blanching more pronounced cycloplegic effect and Phenylephrine is available in either of conjunctival blood vessels, and its a longer recovery period (Figure 2). 2.5 per cent or 10 per cent preservative- use may be associated with upper lid free single-use Minims. Compared with retraction due to influence on Müller’s Phenylephrine tropicamide, dilation with phenylephrine muscle. It is particularly important to Sympathomimetics acting on the is slightly slower with maximal dilation appreciate that phenylephrine has the adrenoreceptors of the dilator muscle 45-60min after instillation, and the potential for systemic side-effects. While within the iris lead to dilation of the degree of dilation is slightly less. An rare, a significant elevation in blood pupil. Phenylephrine is a synthetic important difference with tropicamide pressure has been reported following drug that is very similar to the natural is that phenylephrine does not abolish the use of phenylephrine 10 per cent neurotransmitter epinephrine, but the light reflex because it does not act eyedrops, and so care should be taken differs in that it is more selective for on the iris sphincter. Recovery is slightly when considering administration to the elderly, or persons known to have uncontrolled hypertension or severe cardiovascular disease. Additionally, Multiple-choice questions – take part at opticianonline.net exaggerated responses may occur due to reduced bioelimination in individuals Which of the following drugs is not an Which of the following drugs has the using MAO inhibitors, such as the 1anticholinergic? 4least effect on accommodation? antidepressant phenelzine (Nardil). Drug A Atropine A Tropicamide manufacturers also note that the pressor B B Cyclopentolate response of adrenergic agents may be C Tropicamide C Tropicamide D Phenylephrine D Phenylephrine potentiated by tricyclic antidepressants, propranolol, reserpine, guanethidine, How is phenylephrine eliminated in the Which of the following drugs could raise methyldopa, and atropine-like drugs. ● 2eye? 5blood pressure? A Metabolised by the liver A Atropine References B Absorbed by B Cyclopentolate 1 Mitry D et al. The epidemiology of C Oxidised by enzymes C Tropicamide rhegmatogenous retinal detachment: D Diffuses into the blood D Phenylephrine geographical variation and clinical associations. Br J Ophthalmol, 2010;94: 678-84. Which of the following drugs acts the Which of the following is expected to 2 Marchini G et al. Comparative Study of the 3fastest? 6give the best dilation? Effects of 2% , 10% Phenylephrine, A Atropine A Tropicamide 1% and 1% Tropicamide on the Anterior Segment. B Cyclopentolate B Phenylephrine 10% Invest Ophthalmol Vis Sci, 2003;44:281-9. C Tropicamide C Tropicamide 1% and Cyclopentolate 1% D Phenylephrine D Tropicamide 0.5% and Phenylephrine 2.5% ● Dr Michael Johnson is an independent prescribing optometrist who owns Johnson & Successful participation in this module counts as one credit towards the GOC CET scheme Furze Optometrists, works in the Glaucoma administered by Vantage and one towards the Association of Optometrists Ireland’s scheme. and Accident & Emergency departments The deadline for responses is September 20 2012 at Bristol Eye Hospital, and maintains the patient website www.eyepedia.co.uk

20 | Optician | 24.08.12 opticianonline.net