Reply: Relative efficacy of intracameral moxifloxacin injection methods

We would like to thank Khachikian and Jones for their interest in our recent article and for their compliments on our previous publications.1 They expressed concern primarily on potential intracameral (IC) moxifloxacin toxicity in phakic eyes. BAIT due to prolonged systemic moxifloxacin administration, usually in intensive care units, was first described by Janet Davis's group, who determined the aqueous and vitreous concentrations of moxifloxacin after topical and systemic administration.2 The ensuing severe pigmentary dispersion (due to moxifloxacin concentration, duration of exposure, and its affinity to melanin-rich tissues) and resultant glaucoma are well-recognized.2 The toxicity level of moxifloxacin to human iris pigment epithelial cells was determined to be 100 μg/mL in cell culture after exposure for 48 hours.3 To our knowledge, the only case secondary to IC administration was reported on April 13, 2016 (ASCRS Cataract/Refractive Eye Connections Digest), by Matthew Runde, MD, but not published until 2019.4 The article recounted the story of a 45-year-old male patient who suffered from unilateral BAIT after a 0.1-mL bolus of undiluted moxifloxacin (500 μg/0.1 mL) was administered IC into the right phakic eye after vitrectomy for floaters. The left eye had previously undergone a similar procedure without IC moxifloxacin and did not experience the BAIT-like syndrome. Increased caution of IC moxifloxacin injection into phakic eyes, as emphasized by Khachikian and Jones, has arisen from this case. There have been no reported cases of BAIT syndrome in millions of newly pseudophakic eyes after IC moxifloxacin injection during cataract surgery. We showed that the aqueous concentration of IC moxifloxacin abates rapidly (half-life = 2.89 hours in pseudophakic eyes). If 500 μg is retained after injection in the anterior chamber (AC) half-volume phakic eye, the initial concentration would be twice as high (2000 μg/mL), but with a shorter calculated half-life (1.44 hours) because of more rapid turnover in the smaller volume (Table 1).5 The reduced AC volume and close apposition of the iris to the lens in the phakic eye enable trapping of the injected drug and make the phakic eye more vulnerable to BAIT with undiluted moxifloxacin administration, especially if injected between the iris and the human lens. When diluted moxifloxacin is injected, the AC concentration gradually approaches the concentration of the injected solution, which is the asymptotic limit with increasing injection volume.1 Table 1. - Moxifloxacin concentrations and duration attained in the aqueous and vitreous of phakic and pseudophakic eyes, assuming that with IC injection, 500 μg remains in the anterior chamber Administration mode (volume) Topical IC, phakic (0.25 mL) IC, pseudophakic (0.5 mL) Oral Concentrations achieved Aqueous (μg/mL)2 2.28 ± 1.23 2000 1000 1.34 ± 0.66 Vitreous (μg/mL)2 0.11 ± 0.05 2 1 1.58 ± 0.80 Duration of concentration Aqueous >100 μg/mL (h)5 0 4.4 4.8 0 Aqueous >10 μg/mL (h)5 0 9 14 0 Aqueous >1 μg/mL (h)5 3.5 14 24 Duration of administration IC = intracameral; pseudophakic = newly pseudophakic with an intracapsular posterior chamber IOLFor the purpose of this table, the moxifloxacin concentration abatement rate for a newly pseudophakic eye was taken to be the same as we previously calculated (abatement every hour to 0.7866 of the concentration of the preceding hour), whereas for the smaller anterior chamber volume of a phakic eye, it calculates to 0.6188 because of the higher aqueous turnover in a smaller space.4 If, however, the undiluted antibiotic becomes trapped between the iris and the lens, the turnover will be much slower. The data mentioned above are, therefore, approximate and to be used to illustrate a comparison only. In summary, IC administration of dilute moxifloxacin seems to be safer, in that the concentration to which the iris may be exposed is lower than undiluted moxifloxacin from the bottle (Table 1). Our recommended injection method yields a curve that flattens out with increased volumes of injection, making achieving a dangerous concentration unlikely, barring dilution errors in preparation, whereas small volume full-strength injection, especially if placed under the iris in a phakic eye, may achieve a trapped toxic concentration.1 As commented by Khachikian and Jones, we agree that heightened caution is warranted when injecting undiluted IC moxifloxacin into phakic eyes.

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