Chapter 42
Ocular Side Effects and Toxicities From Systemic Therapy
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Table 1 presents a list of common drugs and drug classes with ocular side effects. The list of ocular side effects and toxicities presented in Table 2 emphasizes orally administered drugs producing well-documented, nonallergic adverse effects at therapeutic doses. Not included are teratogenic effects.


Table 1. Drugs and Drug Classes with Ocular Side Effects

Antihistamines (H1 antagonists)DiethylcarbamazineMethotrexateRetinoic acid
BiperidenDiphenhydramineMonoamine oxidase inhibitorsSulfonamides
BiphosphonatesDisulfiramNalidixic acidSuramin
BusulfanEstrogen-progestin combinationsOral contraceptivesTetracyclines
ButyrophenonesEthambutolOral hypoglycemicsThioridazine
Carbonic anhydrase inhibitorsEthoxzolamideOxygenTilorone
Cardiac glycosidesFluorouracilOxyphenoniumTopiramate
ChloramphenicolGlucocorticosteroidsPargylineTricyclic antidepressants
CortisoneImipraminePhenytoinVitamin A
Cytarabine (cytosine arabinoside)IodochlorhydroxyquinPrednisone 



Table 2. Therapeutic Use of Drugs with Ocular Side Effects and Toxicities

    Side Effect or Toxicity  
Use Drug Type Dose Reversible? Reference
Acne Isotretinoin Blepharoconjunctivitis 1 mg/kg/d for 4 mo Yes 2, 74–77, 11
    Xerosis   Yes  
    Corneal opacities   Yes  
    Night blindness   Yes  
    Pseudotumor cerebri   Yes  
  Minocycline Pseudotumor cerebri   Yes 127
    Scleral pigmentation   Variable 140–141
  Tetracycline Pseudotumor cerebri 250 mg/d for 4 mo Yes 3, 4, 67, 10
    Pigmented conjunctival cysts   Not stated  
  Vitamin A Pseudotumor cerebri 200,000 U/d for 2 mo Yes 90, 104, 10
Alcoholism Disulfiram Optic neuropathy   No 5
Arthritis Amodiaquine Corneal deposits   No 6, 7, 9–11
  Chloroquine Corneal deposits   Yes  
    Retinal degeneration >200 g No  
  Hydroxychloroquine Corneal deposits   Yes  
    Retinal deposits >200 g No 125, 126
  Gold Corneal deposits   Yes 12, 13, 95
    Lens deposits   Usually Yes  
  D-Penicillamine Myasthenia 250 mg/d for 2 d Yes 14–16
Cancer Busulfan Cataract >2 mg/d for >8 mo Not stated 17, 83
  Cytarabine Corneal epithelial breakdown 6 g/m/d Yes 84, 85
  Fluorouracil Punctal stenosis 2 g/mo for 2 mo Usually no 19, 86–88
  Corneal epithelial breakdown     Yes  
  Interferon Retinopathy >150 million units/year Yes 119–122
  Methotrexate Corneal epithelial breakdown   Yes 82
  cis-Platinum Cortical blindness   Yes 18
  Suramin Corneal deposits 3.2 g Not stated 89
  Tamoxifen Corneal deposits >8.1 g Not stated 21–23
    Retinal deposits   Not stated  
  Tilorone Corneal deposits 8.1 mg/kg/d for 2 mo Yes 20, 24
    Retinopathy   Partial  
  Vincristine Optic neuropathy 48 mg IV in 14 mo No 25–27
    Ophthalmoplegia   Partial  
    Cortical blindness   Yes  
Cardiac arrhythmia Amiodarone Corneal deposits 1 g/d for 8 wk Yes 28, 98–100, 123, 124
    Lens deposits      
    Optic neuropathy   Partial  
  Cardiac glycosides, e.g., digitalis, digoxin, lanatoside-C, perhexiline Altered color perception   Yes 29, 30, 97, 128–129
    Visual hallucinations   Yes  
    Pseudotumor cerebri 400 mg/d for4 mo Yes 31
Contraception Estrogen-progesterone combinations Retinal vascular occlusions   No 32, 33
Convulsions Diazepam Nystagmus   Yes 34
  Phenobarbital Nystagmus   Yes 35
  Phenytoin Nystagmus   Yes 36, 37
  Topiramate Myopia Not dose-related Yes 113, 114
    Acute glaucoma Not dose-related Yes  
  Trimethadione Night blindness   Yes 38
  Vigabatrin Visual field constriction >250 g cumulative No 107–112
Diabetes mellitus          
General anesthetic Oral hypoglycemics Posterior cataract   Not stated 39
Glaucoma Methoxyflurane Retinal deposits 4.5-h inhalation Not stated 40
  Carbonic anhydrase inhibitors, e.g., acetazolamide, ethoxzolamide Myopia Not dose-related Yes 41, 42
    Acute glaucoma Not dose-related Yes  
Hypertension Niacin Maculopathy 3 g/d Yes 78
  Practolol Conjunctival fibrosis >300 mg/d for 6 mo No 43–45
  Chloramphenicol Optic neuropathy >25 mg/kg for >3 mo Usually yes 46
  Diethylcarbamazine Optic neuropathy 1.8 g in 8 d Variable 47
    Retinal pigment epitheliopathy   Variable  
  Ethambutol Optic neuropathy >15 mg/kg/d Usually yes 48, 91, 92
  Iodochlorhydroxyquin Optic neuropathy   No 49, 51
  Nalidixic acid Pseudotumor cerebri 18 g in 18 d Yes 50
  Rifabutin Uveitis >100 gm Yes 135–137
  Sulfonamides Myopia   Yes 8, 103
  Suramin Optic neuropathy   Not stated 52
  Tetracyclines, e.g. minocycline Pseudotumor cerebri   Yes 53
Impotence Sildenafil Altered color perception >100 mg Yes 115–117
Inflammation Glucocorticosteroids, e.g. cortisone, dexamethasone, prednisone, prednisolone Posterior cataract >10 mg/d for2 yr Usually no 54–61
    Ocular hypertension   Yes  
  H1 antihistamines, e.g., chloropheniramine, cyclizine, diphenhydramine, promethazine, tripelennamine Mydriasis   Yes  
    Cycloplegia   Yes 132
Iron overload Deferoxamine Retinopathy >50 mg/kg/d Yes 79–81
Motion sickness Hyoscine Cycloplegia   Yes 130
Muscle spasms Quinine Optic neuropathy 900 mg/d for 8 d Partially 62
    Retinal pigment epitheliopathy   Not stated  
Paget's disease Biphosphonates, e.g., alendronate, pamidronate, etidronate Uveitis   Yes 135, 138–141
Parkinsonism Benztropine Mydriasis   Yes 63–65
    Cycloplegia   Yes  
  Biperiden Mydriasis >2 mg/d   Yes
    Cycloplegia   Yes  
  Bromocriptine Myopia 2.5 mg/d Yes  
  L-Dopa Involuntary eye movements >1 g/d Yes  
Peptic ulcer Antimuscarinics, e.g., belladona tincture, methantheline, oxyphenonium, propantheline Mydriasis   Yes 66
    Cycloplegia   Yes  
Psychiatric disorders Butyrophenones, e.g., haloperidol Nystagmus   Yes 68–70, 106
    Mydriasis   Yes  
    Cycloplegia   Yes  
  Monoamine oxidase inhibitors, e.g., pargyline Involuntary saccades   Yes  
    Nystagmus   Yes  
    Mydriasis   Yes  
    Cycloplegia   Yes  
  Phenothiazines Nystagmus   Yes  
    Mydriasis   Yes  
    Cycloplegia   Yes  
    Involuntary saccades   Yes  
  thioridazine Corneal deposits   Usually yes 69
    Lens deposits 300 mg/d for >3 yr Usually no  
    Retinal degeneration   No  
  chlopromazine Corneal deposits   Usually Yes 70
    Lens deposits 800 mg/d for 1 mo Usually no  
    Retinal degeneration     No
  Tricyclic antidepressants, e.g., imipramine Nystagmus   Yes  
    Mydriasis   Yes  
    Cycloplegia   Yes 131
    Involuntary saccades   Yes  
Respiratory distress Oxygen Retinopathy PaO2 >100 mm Hg Variable 71, 72
  Iodide Blepharitis   Yes 102
    Conjunctivitis   Yes  
Sickle cell disease Cyanate Posterior cataract >25 mg/kg/d for 10 mo   73
Tanning Canthaxanthine Retinal deposits   Yes 133, 134
Urinary bladder irrigation Glycine Blindness 1.5% solution Yes 93, 94

d, day; hr, hours; mo, month; wk, week; yr, year; PaO2, partial pressure of arterial oxygen.


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