Conditional/Unclassified

1. Visual field changes

a.Cecocentral scotomas

b.Arcuate scotoma

2. Optic neuropathy

Clinical significance

Voriconazole has unique ocular side effects. The most common visual complaints are altered or enhanced visual perception, ‘enhanced perception of light’, ‘brighter lights and objects’, blurred or ‘hazy’ vision and photophobia ‘dazzle’ or ‘glare’. The onset of these symptoms occurs within 15–30 minutes after exposure (more rapid with IV than oral) with a mean duration of 30–60 minutes (IV more prolonged than oral). In rare instances these visual phenomena may last 1–2 weeks. With repeat exposure, the incidence and severity of the visual reaction decreases in most patients. The altered visual perceptions are reversible and seldom cause a patient to discontinue using the drug. This reaction occurs in up to 38% of patients, most frequently in the very young and the elderly, and is more pronounced when given IV. Humphrey visual field testing showed overall a slight drop in mean sensitivity, resolving in a few days after the drug was discontinued. Patients are most often unaware of decreased color vision and/or any changes in their visual field. Hallucinations occurred in 4.7% of patients exposed to voriconazole.

The certainty of these visual effects due to voriconazole is a combination of positive rechallenges, high incidences, typical pattern of onset and course, and data to show peaks associated with peak serum levels. The mechanism of voriconazole on the visual system probably is a retinal effect. Possibly, voriconazole may keep the retinal receptors in an artificially ‘light adapted’ state, acting on the mechanism of the phototransductor cascade and/or horizontal cell coupling. The importance of these studies to the ophthalmologist is that all findings to date are reversible and nearly always of short duration. There have been scattered spontaneous reports of optic neuropathy and retinal vascular disturbances but most patients who receive this drug have systemic fungal diseases and are on multiple medications. To date there is no data to prove that these findings are drug related. This is a new drug and long-term follow-up is necessary.

References

Denning DW, Griffiths CEM. Muco-cutaneous retinoid – effects and facial erythema related to the novel triazole agent voriconazole. Clin Exp Dermatol 26: 648–653, 2001.

FDA Antiviral Drugs Advisory Committee, Briefing document for voriconazole (oral and intravenous formulations), 4 October 2001.

Hariprasad SM, Mieler WF, Holz ER, et al. Determination of vitreous, aqueous, and plasma concentration of orally administered voriconazole in humans. Arch Ophthalmol 122: 42–47, 2004.

Herbrecht R, Denning DW, Patterson TF, et al. Open randomized comparision of voriconazole and amphotericin-B followed by other licensed antifungal therapy for primary therapy of invasive aspergillosis­ . Presented at the 4th Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, December 2001.

Martindale: The Complete Drug Reference, 34th edn, Pharmaceutical Press, London, 2005.

Physicians’ Desk Reference, 60th edn, Thomson PDR, Montvale, NJ, pp 2543–2552, 2006.

Rubenstein M, Levy ML, Metry D. Voriconazole-induced retinoid-like photosensitivity in children. Pediatr Dermatol 21: 675–678, 2004.

Class: Antileprosy Agents

Generic name: Clofazimine.

Proprietary name: Lamprene.

Primary use

This phenazine derivative is used in the treatment of leprosy and also as an anti-inflammatory in psoriasis, discoid lupus and pyoderma gangrenosum.

Ocular side effects

Systemic administration

Certain

1. Ocular irritation

2. Decreased vision

3. Eyelids or conjunctiva

a.Pigmentation (red-brown)

b.Discoloration of lashes

c.Perilimbal crystalline deposits 4. Tears

a.Discoloration

b.Crystalline drug in tears

c.Aggravation of keratoconjunctivitis sicca 5. Cornea – polychromatic crystalline deposits 6. Photosensitivity

7. Retina

a.Variable macular pigmentary changes

b.Bull’s-eye maculopathy

c.Abnormal ERG

8. Iris – crystalline deposits

Possible

1. Lens – bluish discoloration

Clinical significance

This phenazine derivative can cause dose-related ocular changes mimicking those of choloroquine. Reversible reddish pigmentation of the skin, conjunctiva and cornea can be seen. Polychromatic crystals have been found in the tear film, giving it a reddish appearance. Findings include fine, reddish-brown subepithelial corneal lines and perilimbal crystalline deposits seen on biomicroscopy. These crystals have been seen on the iris and possibly the lens. This rarely interferes with vision, and the crystalline deposits can disappear within a few months to many years after clofazimine has been discontinued. It is unclear if this drug can cause keratoconjunctivitis sicca. It is more likely that the crystals act as an aggravation in patients with clinical or subclinical ocular sicca. These crystals may give a foreign body sensation and symptomatology consistent with a sicca-like syndrome. In one series, up to 50% of patients had some form of conjunctival pigmentation, 12% had variable changes in their vision, 25% had ocular irritation and 32% had crystals in their tears (Kaur et al 1990). Craythorn et al (1986), Cunningham et al (1990) and Forester et al (1992) reported that this drug can produce bull’s-eye maculopathy. Visual loss can be permanent, even if the drug is discontinued.

References and Further Reading

Craythorn JM, Swartz M, Creel DJ. Clofazimine-induced bull’s-eye retinopathy. Retina 6: 50, 1986.

Cunningham CA, Friedberg DN, Carr RE. Clofazamine-induced generalized retinal degeneration. Retina 10(2): 131–134, 1990.

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