Ocular Adverse Effects of Common Medications

Mohamed Morgan

Introduction

Many commonly prescribed medications doctors can adversely affect the eye. These effects range from mild and reversible symptoms, such as dryness and blurred vision, to severe and potentially irreversible conditions including optic neuropathy and retinopathies. Early recognition of medication-related ocular pathology is essential for healthcare professionals, as timely intervention can mitigate vision loss. This review outlines frequently prescribed medications and their associated ocular adverse effects.

Quinine

Important adverse effect

  • Acute retinal toxicity

An antimalarial typically used to treat malarial infections but it is also nocturnal leg cramps. Acute quinine toxicity can result in acute retinal toxicity, which can result in irreversible blindness (1).

Hydroxychloroquine and Chloroquine

Important adverse effects

  • Bull’s-eye maculopathy
  • Irreversible retinal toxicity with long-term use. Increased risk with concurrent tamoxifen use.

Antimalarial agents which are more commonly used in rheumatologic conditions such as Rheumatoid arthritis and Systemic Lupus erythematosus. Hydroxychloroquine binds to melanin and accumulates in the retinal pigment epithelium (RPE). This accumulation disrupts RPE metabolism and reduces phagocytosis of the photoreceptor outer segments, ultimately leading to RPE atrophy and photoreceptor loss (2).

Patients who have been receiving treatment for more than 5 years or at doses greater than 5mg / kg / day are at an increased risk of retinal toxicity and therefore require annual screening (3).

Corticosteroids

Important adverse effects

  • Posterior subcapsular cataracts (long-term use)
  • Steroid-induced glaucoma due to increased intraocular pressure
  • Increased susceptibility to ocular infections e.g. herpes simplex keratitis

Corticosteroids are amongst the most widely used medications in clinical practice; However, prolonged use carries well-recognised ocular complications. The risk of steroid-induced glaucoma is related to the potency and duration of steroid use (4). Long-term steroid use also increases the risk of cataract development, likely due to steroid-induced gene transcription changes within the lens epithelial cells (5). Additionally, steroids impair wound healing and down-regulation of the immune system, thus increasing susceptibility to ocular infections such as corneal ulcers (6).

Ethambutol

Important adverse effects

  • Optic neuritis

This is a bacteriostatic agent that is used as part of the standard treatment regimen for management of active tuberculosis. It is associated with vision-threatening adverse effects, which can occur shortly after initiation. Patients typically present with bilateral, painless, loss of central vision and dyschromatopsia (7).

Antipsychotics

Important adverse effects

  • Dry eye
  • Oculogyric crisis

These medications are widely used for several psychiatric conditions including mood disorders, schizophrenia, and bipolar disorder. Ocular adverse effects vary depending on the class of antipsychotics, dosage, and duration of therapy. First-generation antipsychotics (haloperidol, flupentixol, fluphenazine and perphenazine) are more commonly associated with oculogyric crisis, a rare acute dystonic reaction involving the extraocular muscles characterised by involuntary upward deviation of both eyes due to spasms (7). Their anticholinergic effects may also contribute to dry eye disease due to antagonism of the muscarinic receptors.

Amiodarone

Important adverse effects

  • Verticillate keratopathy
  • Optic neuropathy

An anti-arrhythmic agent commonly used for management of tachyarrhythmias and atrial fibrillation. Amiodarone has been known to cause ocular toxicity, most commonly, corneal deposits known as verticillate keratopathy (whorl keratopathy). This is characterised by a fine golden-brown corneal epithelial deposit. These deposits are typically asymptomatic and do not impair vision (8).

Long-term use of amiodarone can result in optic neuropathy which can take several months to resolve following cessation of therapy (8).

Isotretinoin

Important adverse effects

  • Dry eye
  • Blepharoconjunctivitis
  • Reduced night vision

A derivative of retinoic acid that is commonly prescribed for the treatment of nodulocystic acne. It is thought to reduce the size of sebaceous glands and sebum production, which can also affect ocular surface lubrication, leading to dry eye disease and meibomian gland dysfunction (9). A rare but serious adverse effect is permanent night blindness, thought to result from impaired rhodopsin regeneration (10).

Sildenafil

Important adverse effects

  • Blue-tinted vision
  • Photophobia
  • Blurred vision

A PDE-5 inhibitor used for the management of erectile dysfunction. Although visual side effects are uncommon, it primarily affects colour vision, most often producing blue-tinted vision. Photophobia and blurred vision have also been reported. These adverse effects are typically dose-dependent and resolve within 24 hours (11).

Digoxin

Important adverse effects

  • Xanthopsia (yellow-green vision)

An antiarrhythmic commonly used for management of atrial fibrillation and heart failure. Digoxin toxicity can cause a rare adverse effect known as xanthopsia which is distorted colour perception, in which everything appears yellow (12).

Tamsulosin

Important adverse effects

  • Intraoperative floppy iris syndrome (IFIS)

This is a commonly prescribed alpha-adrenergic blocker used for the management of benign prostatic hyperplasia. It has been associated with intraoperative floppy iris syndrome (IFIS) which occurs during cataract surgery. It is characterised by the triad of 1) flaccid and billowing iris 2) iris prolapse through the surgical incision and 3) intraoperative pupil constriction (13). This can result in complications such as trauma to the iris and posterior capsule rupture. Evidence suggests IFIS can occur several years after discontinuation of tamsulosin (14).

Topiramate

Important adverse effects

  • Acute angle closure glaucoma
  • Nystagmus
  • Diplopia
  • Scleritis

An anti-epileptic drug used in the treatment of epilepsy disorders in adults and children as well as for migraine prophylaxis. It has been reported to cause several ocular side effects, most notably, acute angle closure glaucoma. This can occur within 2 weeks of starting therapy, and more commonly affects women taking, particularly those also taking SSRIs (15). The proposed mechanism involves ciliary body oedema causing forward rotation of the ciliary body and forward displacement of the iris, resulting in angle closure (16).

References

  1. Christoforidis J, Ricketts R, Loizos T, Chang S. Optical coherence tomography findings of quinine poisoning. Clin Ophthalmol. 2011;5:75-80. doi: 10.2147/OPTH.S16026. Epub 2011 Jan 11. PMID: 21407799; PMCID: PMC3033007.
  2. Yam JC, Kwok AK. Ocular toxicity of hydroxychloroquine. Hong Kong Med J. 2006;12:294-304.
  3. Yusuf IH, Foot B, Galloway J, Ardern-Jones MR, Watson SL, Yelf C, et al. The Royal College of Ophthalmologists recommendations on screening for hydroxychloroquine and chloroquine users in the United Kingdom: executive summary. Eye (London, England). 2018;32(7):1168-73.
  4. Francois J. Corticosteroid glaucoma. Ann Ophthalmol 1977; 9: 1075–1080.
  5. James ER. The etiology of steroid cataract. J Ocul Pharmacol Ther 2007;23:403–20.
  6. Srinivasan M, Mascarenhas J, Rajaraman R, Ravindran M, Lalitha P, Glidden DV, Ray KJ, Hong KC, Oldenburg CE, Lee SM, Zegans ME, McLeod SD, Lietman TM, Acharya NR; Steroids for Corneal Ulcers Trial Group. Corticosteroids for bacterial keratitis: the Steroids for Corneal Ulcers Trial (SCUT). Arch Ophthalmol. 2012 Feb;130(2):143-50. doi: 10.1001/archophthalmol.2011.315. Epub 2011 Oct 10. PMID: 21987582; PMCID: PMC3830549.
  7. Chamberlain, P. D., Sadaka, A., Berry, S., & Lee, A. G. (2017). Ethambutol optic neuropathy. Current Opinion in Ophthalmology, 28(6), 545-551.
  8. Raizman M. B., Hamrah P., Holland E. J., Kim T., Mah F. S., Rapuano C. J., & Ulrich R. G. (2017). Drug-induced corneal epithelial changes. Survey of ophthalmology, 62(3), 286–301. 10.1016/j.survophthal.2016.11.008.
  9. Fraunfelder FT, Fraunfelder FW, Edwards R. Ocular side effects possibly associated with isotretinoin usage. Am J Ophthalmol 2001;132:299-305. 10.1016/S0002-9394(01)01024-8
  10. Madke B, Prasad K, Kar S. Isotretinoin-Induced Night Blindness. Indian J Dermatol. 2015 Jul-Aug;60(4):424. doi: 10.4103/0019-5154.160547. PMID: 26288455; PMCID: PMC4533586.
  11. Supriya Arora, Thamolwan Surakiatchanukul, Tarun Arora, Carlo Cagini, Marco Lupidi, Jay Chhablani, Sildenafil in ophthalmology: An update, Survey of Ophthalmology, Volume 67, Issue 2, 2022, Pages 463-487, ISSN 0039-6257, https://doi.org/10.1016/j.survophthal.2021.06.004.
  12. Haruna Y, Kawasaki T, Kikkawa Y, Mizuno R, Matoba S. Xanthopsia Due to Digoxin Toxicity as a Cause of Traffic Accidents: A Case Report. Am J Case Rep. 2020 Aug 8;21:e924025. doi: 10.12659/AJCR.924025. PMID: 32769961; PMCID: PMC7440749.
  13. Gani J, Perlis N, Radomski SB. Urologic medications and ophthalmologic side effects: a review. Can Urol Assoc J. 2012 Feb;6(1):53-8. doi: 10.5489/cuaj.11037. PMID: 22396371; PMCID: PMC3289699.
  14. Chang DF, Campbell JR. Intraoperative floppy iris syndrome associated with tamsulosin. J Cataract Refract Surg. 2005;31:664–73. doi: 10.1016/j.jcrs.2005.02.027
  15. Fraunfelder FW, Fraunfelder FT, Keates EU. Topiramate-associated acute, bilateral, secondary angle-closure glaucoma. Ophthalmology 2004; 111(1):109-11.
  16. Liebmann JM, Weinreb RN, Ritch R. Angle-closure glaucoma associated with occult annular ciliary body detachment. Arch Ophthalmol 1998;116(6):731-5.

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