The question concerns vision disturbances in connection with NSAIDs, especially Voltaren (diclofena

Fråga: The question concerns vision disturbances in connection with NSAIDs, especially Voltaren (diclofenac).

Sammanfattning: A large range of ocular adverse effects in connection with NSAIDs have been reported, such as blurred vision, diplopia, decreased colour vision, optic neuritis, toxic amblyopia, corneal deposits and visual field defects. Generally, these symptoms are considered to occur with a very low incidence and to be reversible after discontinuation of the drug. Transient blurred vision seems to be the predominant ocular side-effect. The mechanism is not quite clear, but could be related to locally diminished microcirculation, due to prostaglandin inhibition. Rare cases have been described of retinopathy induced by NSAIDs which were irreversible or only partly reversible after discontinuation of the drug. No published reports of visual disturbances specifically caused by diclofenac could be found in the literature, but cases have been reported to SADRAC and the WHO.

Svar: A large range of ocular side-effects have been reported in connection with NSAIDs like ibuprofen, indomethacin, ketoprofen, naproxen and oxyphenbutazone (1). These mostly concern decreased vision, but also include diplopia, problems with colour vision, optic neuritis, toxic amblyopia, corneal deposits and visual field defects. According to (1), these adverse ocular events occur with a low incidence, are reversible after discontinuation of the drug and primarily consist of transient blurred vision. However, rarely, optic nerve responses such as the development of central scotomas with markedly reduced vision after one to three weeks therapy with ibuprofen have been described, with vision returning to normal within 3 months after discontinuation of the drug (1). The causal relationship between use of NSAIDs and severe ocular side-effects such as papilloedema, cataracts and macular degeneration seems unclear, due to contradictory reports (1).

The total frequency of side-effects reported after treatment with diclofenac is 12-25 per cent (2). Between 1-8 per cent of these are CNS-related side-effects. According to the manufacturer (3), about half a billion patients have been treated with diclofenac so far, with only a few cases of vision disturbances reported. Up to and including 1988, the manufacturer had received 18 reports of blurred vision, 11 reports of diplopia, two cases of scotoma and one case of amblyopia possibly caused by diclofenac. The mechanism of these side-effects is not known, but could be related to decreased microcirculation due to local prostaglandin inhibition (3).

An extensive literature search, including the databases Medline and Embase, did not reveal any reports concerning ocular side-effects specifically caused by diclofenac. One case report (4) describes visual disturbances associated with use of over-the-counter ibuprofen in three patients suffering from migraine. The dosage varied between 800 mg weekly to 1200 mg daily, for several months. All three patients had subjective and objective decreased vision and two had evidence of bilateral macular oedema. Vision improved within one month after discontinuation of the drug. It was proposed that continued use of NSAIDs in patients suffering from classical migraine could result in persistent retinal ischaemia through a prolongation of vasoconstriction by blocking the inhibitory influences of prostaglandins.

Another report (5) concerns a severe retinopathy in a 33-year-old man who had used indomethacin 200 mg daily for eight years. In this case, there was continued deterioration of his vision following withdrawal of the drug. Although there is a great deal of uncertainty as to what extent indomethacin is retinotoxic, the authors considered this to be a case of severe indomethacin retinopathy.

Of a total number of 370 reports on diclofenac received by the Swedish Adverse Drug Reactions Advisory Committee between 1982 and 1993, 12 concerned ocular side-effects possibly caused by diclofenac: one case of retinal oedema, two cases of visual field defects, one case of conjunctivitis, two of diplopia, three of blurred vision and three of "affected" vision.

A total number of 545 reports of ocular side-effects in connection with diclofenac use has been reported so far to the WHO. Most cases (215) concern "decreased vision" and "eye pain" (105) but cases of blindness and retinal disorders have also been reported. However, these numbers are difficult to evaluate because detailed information is lacking, including concomitant use of other drugs. 1 Fraunfelder, Drug-induced ocular side-effects and drug interaction. 1982; 2nd ed: 135-146 2 Drugline nr 04048 (year 1984) 3 Roland Björkman, Ciba-Geigy, personal communication 4 Nicastro NJ: Visual disturbances associated with over-the-counter ibuprofen in three patients. Ann Ophthalmol 1989; 29: 447-450 5 Graham CM, Blach RK: Indomethacin retinopathy: case report and review. Br J Ophthalmol 1988; 72: 434-438