Ocular Toxicity of Systemic Drugs
Deborah Pavan-Langston
I. General Considerations
Many undesired side effects on the ocular tissues have been reported involving various drugs used for both the treatment of systemic medical disorders and for local ophthalmic problems. The types of adverse effects of drugs on the eye may be mild and transient, such as temporary decreased visual acuity, impairment of accommodation, abnormal pupillary responses, and color vision disturbances. Other effects, such as eye movement abnormalities, glaucoma, cataracts, and retinal damage, may seriously reduce ocular function. To recognize and prevent vision-threatening complications from adverse effects of drug reactions, it is necessary for the clinician to obtain a careful history, with particular attention to specific medications used. The clinician must then be aware of certain oculotoxic drugs and their side effects to recognize the drug-related eye disorder.
II. Pretreatment Examination
For certain drugs with potential ocular toxicity, a careful pretreatment examination should be performed before the drug is administered, particularly if (a) the drug will be used for a long period of time (isoniazid, streptomycin, quinine, and indomethacin), or (b) it is known to have severe toxic effects (ethambutol, hydroxychloroquine, and thioridazine). Patients taking drugs that are not as toxic may not require the complete baseline examination before therapy, but they should undergo frequent monitoring examinations so that if symptoms do arise, the drug can be withdrawn immediately. Reversible effects can likewise be observed while the patient is not taking the drug, and later, after resolution of the effects, the drug regimen may be judiciously reinstituted at a lower dose. The pretreatment examination should include the following steps, which are described in greater detail in Chapter 1.
Visual acuity with glasses. Test acuity screening at near and distance with and without pinhole testing.
Pupillary responses. Test pupil size, briskness of reactions (direct and consensual) to light, and convergence reflex.
Ocular motility examination. Test complete motility in all fields of gaze with ductions, versions, and convergence.
Intraocular pressures. Periodic tonometry should be performed.
Slitlamp examination (biomicroscopy). Drugs may affect the conjunctiva, cornea, and lens during the course of therapy. Loupe or slitlamp examination is indicated. Tear film adequacy should be tested.
Dilated ophthalmoscopy. Drugs may cause changes in the retina, macula, blood vessels, and the optic nerve.
Special examinations for retinal function. Other tests may be performed to provide supplemental data on retinal function. These examinations include
Photography of the fundus.
Electroretinography.
Visual fields.
Color vision tests.
Visual evoked potential.
Fluorescein angiography.
III. Repeat Eye Examinations
should be performed and followed judiciously if there is any clinical change noted during the course of the patient’s therapy.
IV. Ocular Manifestations of Systemic Drug Toxicity
Reduced visual acuity may result from transient changes in refractive errors or anterior or posterior segment toxicity.
Blurred vision may be caused by dilated pupils (mydriasis) and impairment of accommodation (cycloplegia), as well as anterior or posterior segment toxic changes.
Color vision disturbances include hallucination, altered perception, and diminished sensitivity.
Ocular motility abnormalities include neuromuscular myesthenic block, paralytic strabismus, diplopia, and oculogyric crisis.
Conjunctival inflammation and corneal opacification may occur.
Glaucoma may occur in those individuals with shallow anterior chamber angles who use drugs that cause mydriasis, or in deep open angles depending on the offending agent.
More serious are those adverse drug effects that occur in the crystalline lens (cataract) and the optic nerve.
There are still other oculotoxic conditions, such as exophthalmos, retinal hemorrhages, vasculopathy, retinal pigment epitheliopathy, and macular edema.
V. Drugs and their Ocular Toxicity
Tables 16.1,16.2,16.3,16.4,16.5,16.6,16.7,16.8,16.9,16.10,16.11,16.12,16.13,16.14,16.15,16.16,16.17,16.18 represent major drug classifications under which are listed some example drugs and their potential adverse ocular side effects. Also tabulated are associated symptoms and signs according to specific ocular structures:
Analgesics (Table 16.1).
Antiarthritics (Table 16.2).
Anesthetics—general (Table 16.3).
Antihistamines (Table 16.4).
Anti-infectives: antibiotics (Table 16.5).
Antivirals—systemic (Table 16.6).
Antineoplastic agents (Table 16.7).
Cardiovascular drugs (Table 16.8).
Central nervous system (CNS) drugs (Table 16.9).
Dermatologic agents (Table 16.10).
Diuretics and osmotics (Table 16.11).
Gastrointestinal agents (Table 16.12).
Hematologic agents (Table 16.13).
Hormonal agents (Table 16.14).
Immunosuppressant agents (Table 16.15).
Neuromuscular agents (Table 16.16).
Vaccines (Table 16.17).
Vitamins (Table 16.18). For a more extensive listing, see Fraunfelder FT, Fraunfelder FW. Drug-induced ocular side effects, 5th ed. Boston: Butterworth Heineman, 2001.
VI
Examples of drugs in each category are given usually by generic name but occasionally by commercial name for reader orientation. It should be noted that not all drugs in each category have been reported as causing every side effect within that category. The potential for a given side effect in any category, including new drugs that are continuously coming into use, should be borne in mind, however, even if not previously reported for a specific agent.
Abbreviations Used in Tables 16.1,16.2,16.3,16.4,16.5,16.6
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