Many systemic medications are associated with ocular complications. Drugs affecting intraocular pressure include corticosteroids, ketamine, succinylcholine, anticholinergics, heroin, marijuana, topiramate, sulfonamides, and acetazolamide. Systemic drugs linked to cataract formation include corticosteroids and chlorpromazine. Medications such as corticosteroids, chlorpromazine, and amiodarone are associated with corneal abnormalities. Retinal complications may result from systemic drugs such as chlorpromazine, digitalis, ethambutol, chloroquine, hydroxychloroquine, quinine, oral contraceptives, and tamoxifen. An understanding of the ocular side effects of systemic medications aids ophthalmologists in guiding patients toward appropriate and rational use of drugs.
Corticosteroids
Prolonged local, periocular, inhaled, or systemic use of corticosteroids may lead to corticosteroid-induced glaucoma. This condition manifests with characteristics similar to primary open-angle glaucoma, with its mechanism related to increased resistance to aqueous humor outflow through the trabecular meshwork. Since corticosteroid-induced glaucoma can occur at any point during long-term corticosteroid therapy, regular monitoring of intraocular pressure is essential in such patients. Steroids such as fluorometholone, rimexolone, medrysone, and loteprednol have less impact on intraocular pressure compared to prednisolone and dexamethasone, making them preferable choices when steroids are required. Additionally, elevated intraocular pressure may also occur in patients with endogenous hypercortisolism, such as those with Cushing’s syndrome, although intraocular pressure typically normalizes after removal of the causative tumor or hyperplasia.
Prolonged systemic corticosteroid use may also cause cataract formation and worsen or trigger herpes simplex keratitis. Furthermore, systemic corticosteroids are associated with serous retinal detachment and, in severe cases, bullous retinal detachment during the treatment of systemic diseases.
Sedative Drugs
Chlorpromazine, when used at high doses (500 to 1,500 mg/day) over extended periods (3 to 10 years), may induce ocular damage. Manifestations include:
- Eyelids: Blue-gray or purplish discoloration, with exposed conjunctival zones appearing copper-brown.
- Cornea: Lens-like opacities in the lower half of the epithelium or stroma.
- Cataracts: Gray-white deposits or light brown opacity under the anterior capsule.
- Retina: Altered pigmentation and macular pigmentation changes.
Minimizing the daily dosage to below 400 mg may help reduce the risk of ocular harm.
Cardiovascular Medications
Digitalis
Digitalis enhances myocardial contraction and slows heart rate. In a subset of patients, visual disturbances may occur, including blurred vision, altered color perception (e.g., viewing objects as yellow, green, red, or white), photophobia, or flashes of light. In rare cases, central visual loss with scotomas may occur, potentially related to retrobulbar optic neuritis.
Amiodarone
Amiodarone, an antiarrhythmic drug, frequently causes fine deposits in the basal epithelial cells of the cornea, often appearing in a vortex-like pattern. The severity of these corneal changes correlates with the daily dose, with those taking less than 20 mg daily experiencing milder effects. Although the corneal alterations may progress during treatment, vision is rarely affected, and the deposits typically resolve completely after discontinuing the medication.
Antituberculosis Drugs
Ethambutol
Prolonged use of ethambutol, particularly at daily doses exceeding 25 mg/kg, may cause optic neuritis or damage to the optic chiasm, resulting in bitemporal hemianopia. Visual function in some cases may recover after discontinuing the drug.
Rifampicin
Rifampicin, typically used in combination with other antituberculosis medications, may cause tinted tears in colors such as orange, pink, or red. Rarely, visual disturbances are reported.
Anticonvulsants
Topiramate, a sulfamate-substituted monosaccharide, is used in the treatment of epilepsy and depression. Some patients using this medication may develop acute high myopia (greater than −6D) and bilateral acute angle-closure glaucoma. These complications generally occur within one month of initiating topiramate treatment. Ocular findings may include changes in refraction, uniformly shallow anterior chambers with forward displacement of the lens-iris diaphragm, microcystic corneal edema, elevated intraocular pressure (40–70 mmHg), angle closure, and ciliary body/choroidal effusion or detachment. The underlying mechanism involves ciliary body and choroidal effusion, causing zonular relaxation and significant forward movement of the lens-iris diaphragm, leading to secondary acute angle-closure glaucoma and high myopia. Secondary glaucoma can typically be controlled within 24–48 hours after discontinuing topiramate, and myopia may resolve within 1–2 weeks.
Non-Steroidal Anti-Estrogen Drugs
Tamoxifen, commonly used as adjuvant therapy for breast cancer surgery, has been shown to improve survival rates in breast cancer patients. However, even at low doses (20–40 mg/day), ocular toxicity has been reported. This may manifest as white to brown crystalline deposits in the subepithelial cornea, superficial corneal ulcers, cataracts, optic neuritis, intraretinal high-reflective crystalline deposits (with or without macular edema), and pseudo-cystic changes in the macular fovea. These ocular side effects are thought to be related to the estrogenic activity of tamoxifen.
Antimalarial Drugs
Chloroquine
Chloroquine is used to treat acute malaria episodes and also for conditions such as hepatic amebiasis, clonorchiasis, paragonimiasis, connective tissue diseases, and photosensitive disorders. Long-term or high-dose use, especially when the cumulative dose exceeds 100 g or treatment lasts over one year, may result in ocular damage. Between 30% and 70% of patients may develop fine grayish-white deposits in the corneal epithelium or subepithelium encircling the cornea, though only mild blurring of vision typically occurs, which is reversible upon discontinuation. Mild corneal involvement is not considered an indication to stop the drug. However, chloroquine may rarely cause more severe retinal toxicity, leading to central vision loss and concentric narrowing of the peripheral visual field. Fundoscopic findings include macular pigment deposits surrounded by a ring of depigmentation, further encircled by peripheral pigment accumulations, producing a “bull's eye” appearance. In advanced stages, vascular attenuation and optic atrophy with a yellowish waxy disc may occur. Retinal damage caused by chloroquine is irreversible and cumulative. Baseline and periodic assessments of vision, color perception, fundoscopy, and, if necessary, visual fields should be performed before, during, and after using chloroquine.
Hydroxychloroquine, used to treat autoimmune diseases as an antiallergic agent, can cause similar ocular side effects as chloroquine, though the adverse effects are milder. Routine ophthalmological examinations are also necessary during hydroxychloroquine therapy.
Quinine
Quinine, a quinoline-methoxy and alkaloid-based antimalarial drug, may adversely affect nervous tissue and cause retinal vasoconstriction when administered at doses exceeding 4 g within 24 hours. This may result in narrowed visual fields, diplopia, or amblyopia, with rare occurrences of complete blindness. Visual field defects are often partially reversible, though they may become permanent in some cases. Early findings of retinal edema generally resolve after discontinuation of quinine, while optic atrophy represents a late stage. Acute quinine toxicity initially manifests as mydriasis with preserved pupillary light reflexes. In rare cases, vermiform movements of the pupil may be observed, followed by complete blindness. Most cases of vision loss are transient; however, a minority of patients may experience permanent blindness.