Adverse ocular reactions associated with fluoroquinolones: implications for intracameral use

Pubblicato il

Friday, 16 September 2022

Argomento

Eye infections

Oral fluoroquinolones are among the most commonly prescribed classes of antibiotics, as they are indicated for the treatment of a variety of conditions, including intra-abdominal infections, community-acquired pneumonia, bacterial skin infections, acute bacterial exacerbations of chronic bronchitis, active tuberculosis and, in the ophthalmic area, conjunctivitis.

However, some adverse effects associated with the systemic use of fluoroquinolones have been known for several years, which include severe adverse reactions affecting the musculoskeletal system (tendonitis, tendon rupture, myalgia, muscle weakness, arthralgia, joint swelling and gait disturbance) and the peripheral and central nervous system (peripheral neuropathy, insomnia, depression, fatigue and memory impairment), as well as impairment of vision, hearing, smell and taste.

Fluoroquinolones and the risk of uveitis

In a 2004 report on moxifloxacin (a third-generation, broad-spectrum fluoroquinolone with high bioavailability, approved in 1999 by the FDA), uveitis was reported as one of the adverse effects of fluoroquinolones, which was also confirmed as a side effect in later studies.

A review of clinical cases from comprehensive registries, including those of the World Health Organisation and the US Food and Drug Administration, found 40 cases of uveitis secondary to the administration of fluoroquinolones, of which 25 were attributed to tomoxifloxacin.

Several case reports have also highlighted the association of fluoroquinolone use with uveitis, particularly with regard to the use of oral moxifloxacin. Uveitis often occurs following the first administration and, probably, the mechanism of toxicity is determined by direct toxic effects on the iris and ciliary body.

Other ocular adverse reactions following systemic therapy with fluoroquinolones have also been described, including bilateral acute iris depigmentation (BADI, an eye condition also reported following COVID-19 infection) and bilateral acute iris transillumination (BAIT).

Restrictions and precautions for use introduced by AIFA for the prescription of fluoroquinolone antibiotics

Although there is still a lack of consensus on the aetiology of the adverse effects of fluoroquinolones, the Italian Medicines Agency (AIFA), in collaboration with the European Medicines Agency (EMA), in a note dated April 2019, following a re-evaluation of the benefits and risks of all quinolone and fluoroquinolone antibiotics, decided to withdraw medicines containing cinoxacin, flumechin, nalidixic acid and pipemidic acid from the market.

Furthermore, in the note, AIFA recommends that fluoroquinolones should no longer be prescribed for the treatment of non-serious or self-limiting infections and that they should be prescribed with particular caution in older patients.

AIFA also advises to discontinue fluoroquinolone antibiotics immediately at the first signs of adverse reactions and not to prescribe them concomitantly with corticosteroids, as co-administration could exacerbate fluoroquinolone-induced tendinitis or tendon rupture.

New evidence of adverse effects for intracameral use of fluoroquinolones

The off-label intracameral use of moxifloxacin (ICM), a fluoroquinolone, is common in the prophylaxis of post-operative endophthalmitis, as it has shown efficacy in reducing this complication in cataract surgery in several studies.

However, some recent studies, seem to suggest that moxifloxacin may be toxic to iris melanocytes and retinal vascular cells. Indeed, unilateral forms of BADI and BAIT have been reported following intracameral ophthalmic use of this fluoroquinolone.

Affected patients presented with photophobia and loss of accommodation, which can be irreversible and cause visual disability. Atonic pupils, synechiae, elevated intraocular pressure, cataracts and glaucoma were also observed, requiring surgery in some cases.

Although no conclusive data on causation are currently available between these adverse effects and the intracameral use of moxifloxacin, it is necessary to reassess the risks and benefits of future ICM use until these mechanisms are clarified, also in light of previous observations on the use of fluoroquinolones. Moreover, there are effective and safe alternatives in the control of post-operative inflammation after cataract surgery, such as the use of aminoglucoside/dexamethasone combinations, which represent the 'gold standard' of therapy.

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