ACCOMMODATIVE DYSFUNCTION accounts for some of the most common complaints in the eyecare setting. We often attribute this dysfunction to age-related changes, such as presbyopia, and environmental factors, such as excessive electronic device use and even dry eye and cataract formation. However, it is important to remember that a wide range of medications can also affect accommodation as a result of mydriasis, ciliary muscle inhibition, or both. These medications include anticholinergics, tricyclic antidepressants (TCAs), antihistamines, decongestants, sympathomimetics, illicit drugs, neurotoxins, anti-parkinsonians, muscle relaxants, and anticonvulsants. In this article, we review some of the most commonly used medications that lead to accommodative dysfunction and their impact on the aging eye.

Anticholinergics

Anticholinergics are a frequently prescribed drug class that affects the accommodative system, circulation, respiration, and alertness. There are more than 600 medications that have anticholinergic effects. These drugs work by blocking the neurotransmitter acetylcholine in the central and peripheral nervous system. This action inhibits the parasympathetic nervous system more than sympathetic nervous system activation. In the eye, anticholinergics block activation of the sphincter muscle of the iris and the ciliary muscle of the lens. This effect results in both mydriasis and cycloplegia and therefore disrupts accommodation and increases intraocular light scatter.¹

Anticholinergics are used in the treatment of many diseases, including urinary incontinence, Parkinson’s disease, respiratory disorders, cardiovascular disease, cholinergic toxicity, peptic ulcers, irritable bowel syndrome, psychiatric conditions, and many others.

There are many additional medications with anticholinergic properties that can affect accommodation. Medications for overactive bladder, such as oxybutynin, can result in reduced accommodative ability.² Additionally, medications like scopolamine, which can be used to treat motion sickness, can cause accommodative insufficiency.³ Medications for Parkinson’s disease, such as levodopa, can have strong anticholinergic effects.^4,5 There are also types of anticholinergics that are used in the treatment of asthma, including nebulized ipratropium.⁶ Commonly used first-generation antihistamines, such as diphenhydramine, can have anticholinergic effects that result in accommodative insufficiency.^3,7,8 Anticholinergics are commonly prescribed but moreso in individuals older than 40, so discussing these medications’ effects should be part of your patient education regarding visual function and expectations.

Psychotropic Agents

Psychotropic medications, which have anticholinergic properties, can cause a wide range of ocular effects involving every structure in the eye. Of these effects, accommodative dysfunction is mostly linked to TCAs and low-potency antipsychotics.^9,10 In fact, TCAs cause transient blurred vision in up to one-third of patients.⁹ Examples of TCAs include amitriptyline, amoxapine, desipramine, doxepin, imipramine, nortriptyline, protriptyline, and trimipramine. Examples of low-potency antipsychotics include chlorpromazine and thioridazine.

To a lesser extent, selective serotonin reuptake inhibitors (SSRIs) may also affect accommodation. The SSRI with the most anticholinergic properties, and thus the most likely to affect accommodation, is paroxetine.¹¹ Other common SSRIs, such as duloxetine, fluoxetine, citalopram, escitalopram, and sertraline, have a lesser anticholinergic effect and will be less likely to affect accommodation, but they can induce early presbyopia in some.

Another potential class of psychotropic medications that can affect accommodation are methylphenidate and amphetamine-based psychostimulants.¹² These medications are commonly prescribed in the treatment of attention-deficit/hyperactivity disorder. Examples of methylphenidate psychostimulants include the brand-name drugs Ritalin and Concerta. Examples of amphetamine-based psychostimulants include Vyvanse (lisdexamfetamine) and the brand-name drug Adderall. These medications are frequently prescribed in young people, but up to 4% of the population has clinically significant ADHD, so many adults are being treated with these medications as well.¹³

Neurotoxins

Botulinum toxin is commonly used to treat migraine and has numerous cosmetic applications. Botulinum toxins can cause pupil dilatation by uptake into the parasympathetic neurons at the level of the ciliary ganglion or the parasympathetic neuromuscular junctions in the sphincter pupillae of the iris. There are numerous cases documenting the mydriatic effect of botulinum if injected intracamerally or near the ciliary ganglion.^14,15 This injected drug can impact visual function, so be sure to ask patients about use of this injectable. They may not think to provide this information on their medication list.

Illicit and Misused Prescribed Drugs

There are numerous drugs that can cause mydriasis or accommodative dysfunction, so it is important to ask patients about use of these substances as well. Cocaine, methamphetamine, lysergic acid diethylamide (LSD), and marijuana can all cause mydriasis and therefore affect visual function. Amphetamine, methamphetamine, and 3,4 methylenedioxymethamphetamine (MDMA, ecstasy), as well as other psychostimulants, such as cyclazodone, 4-methylaminorex, and prescription stimulants, have similar effects. These effects can be dramatic in the aging eye if presbyopia and cataract formation are concurrently present.

Cyclazodone (n-cyclopropylpemoline), a novel stimulant drug that produces stimulating and focus-enhancing effects similar to dexamphetamine by increasing release of dopamine, noradrenaline, and serotonin, also causes accommodative dysfunction.

Prescription stimulants include amphetamines, methylphenidate for attention-deficit hyperactivity disorder, and nasal decongestants, such as pseudoephedrine, phenylephrine, promethazine, phenylpropanolamine, and oxymetazoline. These drugs can be abused and/or misused, and drug effects on the eye can occur in the form of pupil dilatation and accommodative difficulties.

Hallucinogens

This group of substances includes LSD, psilocybin, phencyclidine (angel dust), and mescaline. These drugs can cause hallucinations, recklessness, sleeplessness, slurred speech, hyperarousal of the central nervous system, loss of coordination, and pupil dilation. An LSD “trip” typically lasts for 6 to 18 hours. Psilocybin is becoming more popular, and studies of the effects of this medicine are increasing, so understanding its ocular accommodative impact is important as well.¹⁶

Herbals and Adaptogens

Trends in natural products, wellness, and prevention should be considered when evaluating patients for accommodative dysfunction. Scopolamine patches are common, but glycopyrrolate antiperspirants and herbals, such as jimson weed, blue nightshade, angel’s trumpet, and ashwagandha (Withania somnifera), can cause pupil dilation and accommodative effects.^17–20

Conclusion

In this review, we provide a high-level overview of medication classes that contribute to accommodative dysfunction, but the number of medications implicated is in the hundreds. It is important to remember that patients affected by presbyopia who take medications that produce even a small degree of pharmacologically-induced mydriasis or cilary muscle impairment may experience significant visual symptoms. The combined effects of presbyopia, cataract, pharmacologically-induced mydriasis, and ciliary body impairment should not be overlooked. Caring for patients older than 40 must include a careful medication history, or refractive correction without patient education might be disappointing.

We have highlighted the major classes of pharmacologic substances likely to be encountered in our patient visits; however, we acknowledge that the list of all potential medications and drugs is extensive and ever-changing. We encourage you to continue to take a careful medical history because vision is affected by a broad range of commonly used medications, herbals, and illicit substances. ■

References

1. Melamed SF. Pharmacology. In: Sedation. 6th ed. Elsevier; 2018:319-358.
2. Wong EY, Harding A, Kowal L. Oxybutynin-associated esotropia. J AAPOS. 2007;11(6):624-625.
3. Barritt LC. Motion sickness. In: Caplan M, ed. Reference Module in Biomedical Sciences. Elsevier; 2014.
4. Compta Y, Tolosa E. Anticholinergic medications. Handb Clin Neurol. 2007;84:121-125.
5. Schapira AHV. Parkinson’s disease. In: Schapira AHV, Byrne E, DiMauro S, et al, eds. Neurology and Clinical Neuroscience. Mosby; 2007:927-960.
6. Marinho S, Custovic A. Management of the asthmatic patient. In: Rich RR, Fleisher TA, Shearer WT, Schroeder H, Frew AJ, Weyand CM. Clinical Immunology: Principles and Practice Expert Consult: Online and Print. 3rd ed. Mosby; 2008:607-626.
7. Ghossein N, Kang M, Lakhkar A. Anticholinergic Medications.; 2022.
8. Gray JP, Ray SD. Anticholinergics. In: Wexler P, ed. Encyclopedia of Toxicology. 3rd ed. Academic Press; 2014:264-266.
9. Richa S, Yazbek JC. Ocular adverse effects of common psychotropic agents: A review. CNS Drugs. 2010;24(6):501-526.
10. Rennie IG. Clinically important ocular reactions to systemic drug therapy. Drug Saf. 1993;9(3):196-211.
11. Nevels RM, Gontkovsky ST, Williams BE. Paroxetine—the antidepressant from hell? Probably not, but caution required. Psychopharmacol Bull. 2016;46(1):77-104
12. Soyer J, Jean-Louis J, Ospina LH, Bélanger SA, Bussières JF, Kleiber N. Visual disorders with psychostimulants: A paediatric case report. Paediatr Child Health. 2019;24(3):153-155.
13. Kolar D, Keller A, Golfinopoulos M, Cumyn L, Syer C, Hechtman L. Treatment of adults with attention-deficit/hyperactivity disorder. Neuropsychiatr Dis Treat. 2008;4(2):389-403.
14. Corridan P, Nightingale S, Mashoudi N, Williams AC. Acute angle-closure glaucoma following botulinum toxin injection for blepharospasm. Br J Ophthalmol. 1990;74(5):309-310.
15. Zheng L, Azar D. Angle-closure glaucoma following periorbital botulinum toxin injection. Clin Exp Ophthalmol. 2014;42(7):690-693.
16. Dhingra D, Kaur S, Ram J. Illicit drugs: Effects on eye. Indian J Med Res. 2019;150(3):228-238.
17. Caglayan HZB, Colpak IA, Kansu T. A diagnostic challenge: Dilated pupil. Curr Opin Ophthalmol. 2013;24(6):550-557.
18. Guharoy SR, Barajas M. Atropine intoxication from the ingestion and smoking of jimson weed (Datura stramonium). Vet Hum Toxicol. 1991;33(6):588-589.
19. Izadi S, Choudhary A, Newman W. Mydriasis and accommodative failure from exposure to topical glycopyrrolate used in hyperhidrosis. J Neuroophthalmol. 2006;26(3):232-233.
20. Firestone D, Sloane C. Not your everyday anisocoria: angel’s trumpet ocular toxicity. J Emerg Med. 2007;33(1):21-24.

Dr. Eid practices in New London, NH, as an associate of Hitchmoth Eyecare. She attended the University of Houston College of Optometry and completed a residency in ocular disease and ocular and refractive surgery at the Oklahoma Medical Eye Group and nJoy Vision in Tulsa, OK.

Dr. Hitchmoth is a nationally recognized, award-winning professor, lecturer, and educator who has authored countless scientific papers, editorials, and book chapters, and has been in practice for 28 years. She had a two-decade tenure as a VA hospital-based executive and provider and owns a private practice and consulting business.