OCULAR COMPLICATIONS OF CERTAIN SYSTEMICALLY ADMINISTERED DRUGS (See Also Chapter 3.)

AMIODARONE

Amiodarone is a benzofuran derivative used to treat cardiac dysrhythmias, particularly Wolff-Parkinson-White syndrome, and angina pectoris. Most patients develop small punctate deposits with a vortex pattern in the basal cell layer of the corneal epithelium (Figure 15-37). The severity of keratopathy is related to the total daily dose and is mild at a dose of less than 200 mg daily. The deposits rarely interfere with vision, and although they progress with continued treatment, even in low dosage, they always resolve completely when treatment is stopped. A small percentage of patients develop thyroid ophthalmopathy, though the mechanism is not fully understood.

ANTICHOLINERGICS (Atropine & Related Synthetic Drugs)

All of these drugs, when given preoperatively or for gastrointestinal disorders, may cause blurred vision in presbyopic patients because of a direct action on accommodation. They also tend to dilate the pupils, so that in patients with narrow anterior chamber angles there is the added threat of angle-closure glaucoma. This is the cause of angle-closure glaucoma (frequently attributed to "nervousness") occasionally seen in patients hospitalized for general surgery.

ANTIDEPRESSANTS

Tricyclic antidepressants and monoamine oxidase inhibitors have an anticholinergic effect and theoretically may exacerbate open-angle glaucoma or provoke an attack of angle-closure glaucoma. However, these side effects are rare in clinical practice.

CHLORAMPHENICOL

Chloramphenicol, in addition to the possibility of causing severe blood dyscrasias, hepatic and renal disease, and gastrointestinal disturbances, can sometimes cause optic neuritis. This is especially true in children. Bilateral blurred vision with central scotomas occurs. Stopping the drug does not always restore vision.

Despite the possibility of toxic optic neuropathy, chloramphenicol may still be required for the treatment of bacterial endophthalmitis. The drug is generally not administered for more than 1 week.

CHLOROQUINE

Chloroquine is an effective antimalarial drug. With high dosage-often 250-750 mg daily administered for months or years-serious ocular toxicity has occurred. Corneal changes were described first and consisted of diffuse haziness of the epithelium and subepithelial area, occasionally sufficient to simulate an epithelial dystrophy. These changes cause only mild blurring of vision and are reversible upon drug withdrawal. Similar changes have been described in patients receiving quinacrine. Minimal corneal involvement is not necessarily an indication for discontinuance of chloroquine therapy.

A less common but more serious ocular complication of long-term chloroquine therapy is retinal damage, causing loss of central vision as well as constriction of peripheral visual fields. Pigmentary changes and edema of the macula, marked alteration of the retinal vessels, and in some cases peripheral pigmentary changes can be seen ophthalmoscopically. Hydroxychloroquine is a derivative of chloroquine that is regularly used in the treatment of collagen diseases (especially systemic lupus erythematosus), rheumatoid arthritis, and chronic skin disease, including discoid lupus and sarcoidosis. The range of ocular complications is the same as with chloroquine, but both their incidence and their severity are greatly reduced. If renal function is normal, routine ophthalmologic screening is probably required only if the daily dose of chloroquine exceeds 6.5 mg/kg or the total duration of treatment exceeds 6 years.

CHLOROTHIAZIDE

Xanthopsia (yellow vision) has been reported in patients taking this oral diuretic.

CONTRACEPTIVES, ORAL

Although numerous reports suggest that in predisposed individuals oral contraceptives can provoke or precipitate ophthalmic vascular occlusive disease or optic nerve damage, it is difficult to establish a definite cause and effect relationship. Optic neuritis, retinal arterial or venous thrombosis, and pseudotumor cerebri have been described in patients taking oral contraceptives. Since there is some uncertainty regarding the possibility of such ocular complications, oral contraceptives should be used only by healthy women with no history of vascular, neurologic, or ocular disease.

CORTICOSTEROIDS

It has been clearly demonstrated that long-term systemic corticosteroid therapy can cause chronic open-angle glaucoma and cataracts and can provoke and worsen attacks of herpes simplex keratitis. Locally administered corticosteroids are much more potent in this respect and have the added disadvantage of causing fungal overgrowth if the corneal epithelium is not intact. Steroid-induced subcapsular lens opacities cause some impairment of visual function but usually do not progress to advanced cataract. Cessation of therapy will arrest progression of the lenticular opacities, but the changes are irreversible. Serous retinal detachments have been associated with systemic corticosteroids, particularly when these agents are used to treat the systemic vasculitides.

OXYGEN

Premature infants who are given any concentration of oxygen in excess of that in the air may develop retinopathy of prematurity (retrolental fibroplasia). These infants should receive only the amount of oxygen necessary for survival. The incidence of the condition was considerably reduced in the 1960s with rigid restriction of oxygen, but despite continued restriction, the incidence has recently risen again. This may be due to prematurity itself (with advanced medical techniques, smaller infants are surviving); the condition is found in 40-77% of infants weighing less than 1 kg.

In adults, administration of hyperbaric oxygen (3 atm) can cause constriction of the retinal arterioles.

PHENOBARBITAL & PHENYTOIN

Ocular complications relate to oculomotor involvement, producing nystagmus and weakness of convergence and accommodation. The nystagmus may persist for many months after cessation of the drug, and the degree of oculomotor abnormality is related to drug dosage. Early abnormalities include disturbance of smooth pursuit.

PHENOTHIAZINES

The phenothiazines usually exert an atropine-like effect on the eye so that the pupils may be dilated, especially with large doses. Of greater clinical significance, however, are the pigmentary ocular changes, which include pigmentary retinopathy and pigment deposits on the corneal endothelium and anterior lens capsule. The corneal and lens pigmentation may cause blurring of vision, but the pigment deposits usually disappear several months after the drug is discontinued. In pigmentary retinopathy, there is a diminution of central vision, night blindness, diffuse narrowing of the retinal arteries, and occasionally severe blindness.

The piperidine group (eg, thioridazine) has a higher risk of causing pigmentary retinopathy, and the maximum daily dose should not exceed 600 mg. The retinal changes are partly reversible under normal circumstances, but in some patients more severe irreversible changes occur at the "safe" dosage level.

The dimethylamine group (eg, chlorpromazine) rarely produces retinal pigmentary changes.

The piperazine group (eg, trifluoperazine) does not produce these retinal complications.

All of these drugs can produce an extrapyramidal syndrome that may involve eye movements. Large doses can provoke profound hypotension, which may produce ischemic optic neuropathy.

Patients receiving large doses or prolonged treatment with phenothiazines should be questioned regarding visual disturbances and should have periodic ophthalmoscopic examinations.

QUININE & QUINACRINE

Quinine and quinacrine, when used in the treatment of malaria, may cause bilateral blurred vision, sometimes following a single dose. There is constriction of the visual field and, rarely, total blindness. The tendency is toward partial recovery, though usually there are permanent peripheral field defects. The ganglion cells of the retina are affected first, presumably as a result of vasoconstriction of the retinal arterioles. Varying degrees of retinal edema occur early. Optic atrophy is a late finding.

SEDATIVE TRANQUILIZERS

When taken regularly, the so-called minor tranquilizers can decrease tear production by the lacrimal gland, thus resulting in ocular irritation because of dry eyes. Tear production returns to normal when the tranquilizers are discontinued.

The principal drugs in this group are meprobamate, chlordiazepoxide, and diazepam.

TAMOXIFEN

Asymptomatic intraretinal crystals are observed in 1-5% of patients who take 20 mg of tamoxifen twice daily. Corneal crystals and optic neuropathy have been reported in patients receiving 80-120 mg daily.

RADIATION

Both optic neuropathy and retinopathy may occur months or years after radiation treatment to the head and neck, particularly to the sinuses or the chiasm. The retinal endothelial cells are damaged, and ischemic retinopathy develops with cotton-wool spots, hemorrhages, and capillary closure. Patients with optic neuropathy present with arcuate field defects, and gadolinium-enhanced MRI reveals characteristic sharply demarcated lesions in the optic nerve. Both conditions progress slowly, and although there is no treatment, anticoagulation or aspirin may halt the process.

FETAL EFFECTS OF DRUGS

The visual pathways of the fetus are occasionally affected by drugs taken by the mother during pregnancy.

Phenytoin may cause optic nerve hypoplasia.

Pigmentary retinopathy has been reported in a child of a mother taking busulfan for acute myeloid leukemia.

Warfarin is teratogenic and may produce a hypoplastic nose, stippled epiphyses, and skeletal abnormalities. Affected children may present with recurrent sticky eyes from obstruction of the nasolacrimal duct secondary to malformation of the nose. Other ocular abnormalities include optic atrophy, microphthalmia, and lens opacities.

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