effects side ocular induced-Drug • 7 t Pa r

Clinical significance

The only side effects of major clinical importance are the lens changes associated with prolonged use of this agent. Lerman

a large-scale population-based epidemiological study showing that patients taking a cumulative dose of more than 400 g of allopurinol­ for longer than 3 years were associated with a twofold increased risk for cataract surgery. This type of study is rare for ophthalmology, but gives definitive proof of an association between allopurinol and cataract formation. Leske et al (1991) implicated the gout medications as second only to steroids as a major risk factor in cataractogenesis. The lens changes seen with allopurinol are anterior and posterior capsular changes with anterior subcapsular vacuoles. With time, wedge-shaped anterior and posterior cortical haze occurs. This may progress to dense posterior subcapsular opacities. While there are a few cases of macular changes reported in the literature and a number in the National Registry, to date there is no clear-cut association between allopurinol and macular changes. Almost 90% of allopurinol systemic drug side effects are skin related. Since the eyelids have some of the thinnest skin on the body, eyelid changes occur.

Recommendations

1. Patients taking allopurinol should wear ultraviolet blocking glasses. This is especially true in occupations, hobbies, etc. with increased sunlight exposure.

2. In keeping with the American Academy of Ophthalmology, patients probably should have an ophthalmic examination every 2 years.

3. Ultraviolet blocking lenses should decrease the incidence of lens changes and eyelid changes secondary to the photosensitivity­ effects of this drug. While there is no proof that the drug causes macular changes, the lens may protect the macula as well.

References and Further Reading

Dan M, et al. Allopurinol-induced toxic epidermal necrolysis. Int J Dermatol 23: 142, 1984.

Fraunfelder FT, Lerman S. Allopurinol and cataracts. Am J Ophthalmol 99: 215, 1985.

Fraunfelder FT, et al. Cataracts associated with allopurinol therapy. Am J Ophthalmol 94: 137, 1982.

Garbe E, Suissa S, LeLorier J. Exposure to allopurinol and the risk of cataract extraction in elderly patients. Arch Ophthalmol 116: 1652–1656, 1998.

Jick H, Brandt DE. Allopurinol and cataracts. Am J Ophthalmol 98: 355, 1984.

Laval J. Allopurinol and macular lesions. Arch Ophthalmol 80: 415, 1968. Lerman S, Megaw JM, Gardner K. Allopurinol therapy and human catarac-

togenesis. Am J Ophthalmol 94: 141, 1982.

Leske MC, Chylack LT, Wu S. The lens opacities case-control study. Risk factors for cataract. Arch Ophthalmol 109: 244–251, 1991.

Pennell DJ, et al. Fatal Stevens-Johnson syndrome in a patient on captopril and allopurinol. Lancet 1: 463, 1984.

Pinnas G. Possible association between macular lesions and allopurinol. Arch Ophthalmol 79: 786, 1968.

Generic name: Colchicine.

Proprietary name: Multi-ingredient preparations only.

Primary use

This alkaloid is used in the prophylaxis and treatment of acute gout. It is also used for treating familial Mediterranean fever, Behçet’s disease, rheumatoid arthritis and primary cholangitis.

Ocular side effects

Systemic administration

Certain

1. Reduction or inhibition of fibrosis

a.Delays wound healing

b.Enhances filtration surgery success

Probable

1. Inhibition of mitosis and migration of epithelial cells with delayed healing

a.Dellen

b.Corneal erosion

c.Corneal ulcers

d.Conjunctival wound, i.e. strabismus surgery

Possible

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

2. Papilledema – toxic states

3. Eyelids or conjunctiva

a.Stevens-Johnson syndrome

b.Toxic epidermal necroylsis

Inadvertent ocular exposure

Certain

1. Decreased vision

2. Conjunctival hyperemia

3. Corneal clouding

Clinical significance

Ocular side effects secondary to colchicine, while rare, have clinical importance. Alster et al (1997) and Biedner et al (1977) both warn that cessation of colchicine should be considered in patients who have corneal ulcers, dellen, corneal or conjuctional epithelial defects, or any ocular wounds that are refractory to conventional treatment. While these complications are probably colchicine side effects, most of the proof comes in part from animal data. Vignes et al (1998) described a case of colchicine-induced intracranial hypertension. Dickenson and Yates (2002) described a case of bilateral eyelid necrosis secondary to pseudomonal septicemia brought on by colchicineinduced neutropenia. Optic nerve changes have been found in animals, but to date no cases have been reported to the National Registry.

References and Further Reading

Alster Y, Varssano D, Loewenstein A, et al. Delay of corneal wound healing in patients treated with colchicine. Ophthalmology 104: 118–119, 1997.

Arroyo MP, Saunders S, Yee H, et al. Toxic epidermal necrolysis-like reaction secondary to colchicines overdose. Br J Dermatol 150: 581–588, 2004.

Biedner BZ, et al. Colchicine suppression of corneal healing after strabismus surgery. Br J Ophthalmol 61: 496, 1977.

Dickenson AJ, Yates J. Bilateral eyelid necrosis as a complication of pseudomonal septicaemia. Br J Oral Maxillofac Surg 40: 175–176, 2002.

Estable JJ. The ocular effect of several irritant drugs applied directly to the conjunctiva. Am J Ophthalmol 31: 837, 1948.

Heaney D, et al. Massive colchicine overdose: a report on the toxicity. Am J Med Sci 271: 233, 1976.