Eye toxicities of systemic drugs

The administration of drugs can affect all structures and functions of the eye.

Adverse eye effects may be related to the pharmacodynamic or pharmacokinetic action of a drug.

Systemic drugs may cause temporary visual disturbance and permanent vision loss.

Aqueous humor maintains intraocular pressure and serves as protection and drains through Schlemm’s canal.

Impairment of aqueous fluid drainage can result in glaucoma, as can drugs that modify its production or drainage.

Drugs can cause contraction of the pupil leading to reduction in pupil size, miosis, which typically occurs in situations of bright light exposure and is controlled by the parasympathetic nervous system.

Cholinergic drug activity leads to miosis.

Mydriasis is the dilation of the pupil and is controlled by the sympathetic nervous system.

Cholinergic agents such as pilocarpine would cause miosis.

Pilocarpine leads to mydriasis,

Amiodarone associated with a range of ocular toxicities, the most common being corneal deposits and colored halos around lights.

Optic neuropathy has also been seen with amiodarone therapy.

Corneal deposits or keratopathy with amiodarone therapy is both time- and dose-dependent.

Corneal deposits and keratathy with amiodarone is seen in 69% to 100% of patients.

Deposits, usually bilateral, are a result of complexes formed with the drug and phospholipids. and normally do not result in visual impairment.

Following amiodarone discontinuation, it takes 3 to 20 months for the deposits to resolve.

Optic neuropathy occurs less than 2% with amiodarone administration, but can lead to vision loss.

Amiodarone optic neuropathy has a gradual onset with slow progression that can ultimately result in bilateral vision loss and disc swelling.

Amiodarone optic neuropathy can lead to permanent visual loss.

Amiodarone optic toxicity includes eyelid irritation, cysts, and dry eyes.

Recommended patients receive a baseline ophthalmic examination prior to initiation of amiodarone therapy, with repeat examinations every 6 months in the first year and every 12 months thereafter.

Topiramate can cause adverse effects including: acute angle-closure glaucoma with elevations in intraocular pressure.

Both chloroquine and hydroxychloroquine carry a risk for ophthalmic toxicity, causing a loss of visual acuity and vision loss characterized by bilateral bull’s-eye maculopathy seen on ophthalmic examination.

Risk for hydroxychloroquine retinopathy increases as treatment duration approaches 5 to 7 years, when the risk for retinopathy approaches 1%.

Cumulative doses of 1,000 g or daily doses above 400 mg per day also lead to a greater risk for toxicity.

Patients with underlying renal or hepatic disease are at higher risk for toxicities from increased drug levels.

Elderly patients and those with preexisting retinal and macular disease are at higher risk since they may be more prone to developing ophthalmic complications

Currently, there is no treatment for hydroxychloroquine-induced retinopathy.

Discontinuation can help stop progression, but damage may not be reversible.

Screening and risk evaluation are the key to limiting ocular toxicity.

Prior to starting hydroxychloroquine, patients should undergo a baseline ophthalmic examination.

Bisphosphonate inflammatory reactions include conjunctivitis, uveitis, scleritis, episcleritis, and keratitis.

Bisphosphonate toxicity may be a result of bisphosphonate secretion into tears, leading to irritation of mucous membranes and cytokine release.

Most cases of conjunctivitis resolve without treatment, but in rare cases, an ophthalmologically administered NSAIDs may be needed.

Uveitis usually requires ocular or systemic medication for treatment and may require discontinuation of the bisphosphonate.

In cases of episcleritis, ocular medication may be needed but the bisphosphonate can be continued.

If scleritis occurs, bisphosphonate discontinuation is required for symptom resolution.

Ethambutol used in the treatment of tuberculosis, and works by inhibiting synthesis of metabolites and impairing cell metabolism in susceptible mycobacteria.

It is often used as part of a four-drug combination with isoniazid, rifampin, and pyrazinamide.

Several ocular adverse events are associated with the use of ethambutol, the most severe being optic neuritis, and other ocular events include color vision changes and visual-field defects.

Ocular toxicity is dosage-related, with patients receiving higher doses at increased risk.

Optic neuropathy can be seen in up to 50% of patients receiving doses of 60 to 100 mg/kg/day, 5% to 6% with doses of 25 mg/kg/day and 1% with doses 15 mg/kg/day.

Patients who receive ethambutol for a longer period of time are also at higher risk.

Visual problems generally appear after 4 to 12 months of treatment with ethambutol, much after the normal duration of use for most patients.

Ethambutol is cleared renally, by both glomerular filtration and tubular secretion; thus,

Renal impairment can lead to increased drug levels of ethambutal and the development of toxicity.

Baseline visual acuity measurements and color discrimination testing are recommended for all patients on ethambutal.

Monthly ophthalmic exams may be indicated for patients who receive dosages above 15 mg/kg/day or patients receive treatment for over 2 months.

Ethambutol should be discontinued if visual symptoms occur.

The phosphodiesterase type 5 (PDE5) inhibitors sildenafil, vardenafil, and tadalafil are effective for the treatment of erectile dysfunction through inhibition of cyclic guanosine monophosphate.

PDE5 inhibitors are associated with ocular adverse events, most commonly changes in color perception and blurred vision.

PDE5 inhibitor ocular events are related to inhibition in the retina, and PDE6, located in photoreceptors of the rods and cones.

Sildenafil can lead to 10% inhibition of PDE6,.

PDE5 inhibitor

Some events have been classified as dose-dependent. including a change in color perception, blurred vision, changes in light perception, photophobia, and eye pain.

The onset of ocular events with PDE5 inhibitors starts within 15 to 30 minutes and peaks 60 minutes after administration.

PDE5 inhibitors ocular events have not led to permanent changes in the perception of color.

Cases of anterior ischemic optic neuropathy have also been reported following the use of PDE5 inhibitors, however, it is not been confirmed as a certain relationship.

Ocular adverse events from PDE5 inhibitors class are generally benign and transient.

Tamsulosin is a selective alpha1A antagonist commonly used for the treatment of BPH and other selective alpha1A antagonists, such as silodosin, have been associated with intraoperative floppy iris syndrome (IFIS).

Intraoperative floppy iris syndrome (IFIS) is seen mainly during cataract surgery and to a lesser extent in glaucoma surgery.

Niacin, may be associated with cystoid macular edema and blurred vision.

Chamomile, when used topically around the eye, can cause severe conjunctivitis and angioedema.

Echinacea, used orally can cause eye irritation and conjunctivitis.

Ginkgo biloba, used orally for memory, has resulted in hyphema and retinal hemorrhages, likely linked to the inhibition of platelet aggregation.

Licorice, used orally for anti-inflammatory and antiplatelet effects, has been associated with cases of transient visual loss following consumption of large quantities.

Leave a Reply

Your email address will not be published. Required fields are marked *