effects side ocular induced-Drug • 7 t Pa r

Ocular side effects

Systemic administration

Certain

1.Decreased or blurred vision

2.Eyelids or conjunctiva

a.Allergic reactions

b.Erythema

c.Conjuctivitis – non-specific

d.Steven-Johnson syndrome

e.Angioneurotic edema

f.Blepharospasm (lorazepam)

3.Diplopia

4.Decreased corneal reflex (clorazepate, diazepam)

5.Extraocular muscles

a.Nystagmus – horizontal or gaze evoked

b.Decreased spontaneous movements

c.Abnormal conjugate deviations

d.Jerky pursuit movements

e.Decreased saccadic movements

f.Oculogyric crises

g.Paralysis

6.Decreased accommodation

7.Decreased depth perception (chlordiazepoxide)

8.Visual hallucinations

9.Problems with color vision – color vision defect

(lorazepam, oxazepam) 10. Photophobia

11. Abnormal EOG (diazepam)

Possible

1.Pupils

a.Mydrasis – weak

b.Decreased reaction to light

c.Miosis (midazolam)

d.May precipitate narrow angle glaucoma

2.Lacrimation

3.Non-specific ocular irritation

a.Ocular pain

b.Burning sensation

5.Subconjunctival or retinal hemorrhages secondary to drug-induced anemia

6.Loss of eyelashes or eyebrows (clonazepam)

Conditional/Unclassified

1. Brown lens opacification (diazepam)

2. Retinopathy (clonazepam)

3. Visual field defects (diazepam)

Ocular teratogenic effects

Probable

1. Increased incidences strabismus (diazepam)

2. Epicanthal folds (oxazepam, diazepam)

3. ‘Slant eyes’ (oxazepam, diazepam)

Clinical significance

Benzodiazepine derivatives are often used in combination with other drugs, so clear-cut drug-induced ocular side effects are difficult to determine. However, ocular side effects are seldom of clinical importance and most are reversible. At therapeutic ­dosage levels, these agents may cause decreased corneal reflex, decreased accommodation, decreased depth perception and abnormal extraocular muscle movements. Speeg-Schatz et al (2001) and others have shown that single dosage in susceptible

individuals can cause phorias, diplopia and fusional impairment. There are reports in the National Registry that diplopia was severe enough to require discontinuing the drug. All drugs in this class appear to cross-react with allergic conjunctivitis since they have the metabolite desmethyldiazepam, a probably antigen, in common. This may give a type I immune reaction. Typically, the allergic conjunctivitis occurs within 30 minutes of taking the drug, with the peak reaction occurring within 4 hours and subsiding in 1 to 2 days. Symptoms include blurred vision, photophobia, burning, tearing and a foreign body sensation. Contact lens wearers have confused this adverse drug effect with poorly fitted lenses. To what degree these benzodiazepine derivatives cause pupillary dilatation is uncertain. There are cases in the literature (Kadoi et al 2000) and the National Registry of patients who developed a narrow-angle attack after receiving one of these drugs. This may be a chance event since these groups of drugs have minimal pupillary effect. The report of maculopathy secondary to gazing into a bright video camera light in two patients taking triazolam may or may not be a drug-enhanced photophic effect.

Diazepam taken over many years has been reported to cause the lens to become brown (Pau 1985) or in high dosage (100 mg) to cause significant visual field loss (Elder 1992).

References and Further Reading

Berlin RM, Conell LJ. Withdrawal symptoms after long-term treatment with therapeutic doses of flurazepam: A case report. Am J Psychiatry 140: 488, 1983.

Elder MJ. Diazepam and its effects on visual fields. Aust NZ J Ophthalmol 20: 267–270, 1992.

Gatzonis Karadimas P, Gatzonis Bouzas EA. Clonazepam associated retinopathy. Eur J Ophthalmol 13: 813–815, 2003.

Kadoi C, Hayasaka S, Tsukamoto E, et al. Bilateral angle closure

glaucoma and visual loss precipitated by antidepressant and antianxiety agents in a patient with depression. Ophthalmologica 214: 360–361, 2000.

Laegreid L, et al. Teratogenic effects of benzodiazepine use during pregnancy. J Pediatr 114: 126–131, 1989.

Laroche J, Laroche C. Modification of colour vision. Ann Pharm Francaises 35: 5-6, 173–179, 1977.

Lutz EG. Allergic conjunctivitis due to diazepam. Am J Psychiatry 132(5): 548, 1975.

Marttila JK, et al. Potential untoward effects of long-term use of flurazepam in geriatric patients. J Am Pharm Assoc 17: 692, 1977.

Miyagawa M, Hayasaka S, Noda S. Photic maculopathy resulting from the light of a video camera in patients taking triazolam. Ophthalmologica 208(3): 145–146, 1994.

Nelson LB, et al. Occurrence of strabismus in infants born to drug-dependent women. Am J Dis Child 141: 175–178, 1987.

Noyes R, et al. A withdrawal syndrome after abrupt discontinuation of alprazolam. Am J Psychiatry 142: 114, 985.

Pau H. Braune scheibenförmige einlagerungen in die lines nach langzeitgabe von Diazepam (Valium). Klin Monatsbl Augenheilkd 187: 219–220, 1985.

Sandyk R. Orofacial dyskinesia associated with lorazepam therapy. Clin Pharm 5: 419, 1986.

Speeg-Schatz C, Giersch A, Boucart M, et al. Effects of lorazepam on vision and oculomotor balance. Binocular Vision Strabismus Q 16: 99–104, 2001.

Tyrer PJ, Seivewright N. Identification and management of benzodiazepine dependence. Postgrad Med J 60(Suppl. 2): 41, 1984.

Vital-Herne J, et al. Another case of alprazolam withdrawal syndrome. Am J Psychiatry 142: 1515, 1985.

Watanabe Y, Kawada A, Ohnishi Y, et al. Photosensitivity due to alprazolam with positive oral photochallenge test after 17 days administration.

J Am Acad Dermatol 40: 832–833, 1999.