Brown Jeremy P, Wing Kevin, Evans Stephen J, Leyrat Clémence, Mansfield Kathryn E, Smeeth Liam, Wong Angel Y S, Yorston David, Galwey Nicholas W, Douglas Ian J
Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, United Kingdom.
JAMA Ophthalmol. 2024 Jul 1;142(7):636-645. doi: 10.1001/jamaophthalmol.2024.1712.
Fluoroquinolone use has been associated with increased risk of uveitis and retinal detachment in noninterventional studies, but the findings have been conflicting and causality is unclear.
To estimate the association of systemic fluoroquinolone use with acute uveitis or retinal detachment, using multiple analyses and multiple databases to increase the robustness of results.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from the Clinical Practice Research Datalink Aurum and GOLD UK primary care records databases, which were linked to hospital admissions data. Adults prescribed a fluoroquinolone or a comparator antibiotic, cephalosporin, between April 1997 and December 2019 were included. Adults with uveitis or retinal detachment were analyzed in a separate self-controlled case series. Data analysis was performed from May 2022 to May 2023.
Systemic fluoroquinolone or comparator antibiotic.
The primary outcome was a diagnosis of acute uveitis or retinal detachment. Hazard ratios (HRs) were estimated in the cohort study for the association of fluoroquinolone prescription with either uveitis or retinal detachment, using stabilized inverse probability of treatment weighted Cox regression. Rate ratios (RRs) were estimated in the self-controlled case series, using conditional Poisson regression. Estimates were pooled across databases using fixed-effects meta-analysis.
In total, 3 001 256 individuals in Aurum (1 893 561 women [63.1%]; median [IQR] age, 51 [35-68] years) and 434 754 in GOLD (276 259 women [63.5%]; median [IQR] age, 53 [37-70] years) were included in the cohort study. For uveitis, the pooled adjusted HRs (aHRs) for use of fluoroquinolone vs cephalosporin were 0.91 (95% CI, 0.72-1.14) at first treatment episode and 1.07 (95% CI, 0.92-1.25) over all treatment episodes. For retinal detachment, the pooled aHRs were 1.37 (95% CI, 0.80-2.36) at first treatment episode and 1.18 (95% CI, 0.84-1.65) over all treatment episodes. In the self-controlled case series, for uveitis, the pooled adjusted RRs (aRRs) for fluoroquinolone use vs nonuse were 1.13 (95% CI, 0.97-1.31) for 1 to 29 days of exposure, 1.16 (95% CI, 1.00-1.34) for 30 to 59 days, and 0.98 (95% CI, 0.74-1.31) for 60 days for longer. For retinal detachment, pooled aRRs for fluoroquinolone use vs nonuse were 1.15 (95% CI, 0.86-1.54) for 1 to 29 days of exposure, 0.94 (95% CI, 0.69-1.30) for 30 to 59 days, and 1.03 (95% CI, 0.59-1.78) for 60 days or longer.
These findings do not support an association of systemic fluoroquinolone use with substantively increased risk of uveitis or retinal detachment. Although an association cannot be completely ruled out, these findings indicate that any absolute increase in risk would be small and, hence, of limited clinical importance.
在非干预性研究中,使用氟喹诺酮类药物与葡萄膜炎和视网膜脱离风险增加有关,但研究结果相互矛盾,因果关系尚不清楚。
通过多种分析方法和多个数据库,评估全身性使用氟喹诺酮类药物与急性葡萄膜炎或视网膜脱离之间的关联,以增强结果的稳健性。
设计、设置和参与者:这项队列研究使用了临床实践研究数据链Aurum和英国黄金初级医疗记录数据库的数据,并与医院入院数据相链接。纳入了1997年4月至2019年12月期间开具氟喹诺酮类药物或对照抗生素头孢菌素的成年人。患有葡萄膜炎或视网膜脱离的成年人在单独的自我对照病例系列中进行分析。数据分析于2022年5月至2023年5月进行。
全身性使用氟喹诺酮类药物或对照抗生素。
主要结局是急性葡萄膜炎或视网膜脱离的诊断。在队列研究中,使用稳定的治疗逆概率加权Cox回归估计氟喹诺酮类药物处方与葡萄膜炎或视网膜脱离之间关联的风险比(HRs)。在自我对照病例系列中,使用条件泊松回归估计发病率比(RRs)。使用固定效应荟萃分析汇总各数据库的估计值。
队列研究共纳入了Aurum数据库中的3001256人(1893561名女性[63.1%];年龄中位数[四分位间距]为51[35 - 68]岁)和GOLD数据库中的434754人(276259名女性[63.5%];年龄中位数[四分位间距]为53[37 - 70]岁)。对于葡萄膜炎,首次治疗时氟喹诺酮类药物与头孢菌素相比的汇总调整后风险比(aHRs)为0.91(95%置信区间,0.72 - 1.14),所有治疗时为1.07(95%置信区间,0.92 - 1.25)。对于视网膜脱离,首次治疗时汇总调整后风险比为1.37(95%置信区间,0.80 - 2.36),所有治疗时为1.18(95%置信区间,0.84 - 1.65)。在自我对照病例系列中,对于葡萄膜炎,氟喹诺酮类药物使用与未使用相比,暴露1至29天的汇总调整后发病率比(aRRs)为1.13(95%置信区间,0.97 - 1.31),30至59天为1.16(95%置信区间,1.00 - 1.34),60天及以上为0.98(95%置信区间,0.74 - 1.31)。对于视网膜脱离,氟喹诺酮类药物使用与未使用相比,暴露1至29天的汇总调整后发病率比为1.15(95%置信区间,0.86 - 1.54),30至59天为0.94(95%置信区间,0.69 - 1.30),60天及以上为1.03(95%置信区间,0.59 - 1.78)。
这些发现不支持全身性使用氟喹诺酮类药物与葡萄膜炎或视网膜脱离风险实质性增加之间存在关联。尽管不能完全排除关联,但这些发现表明,任何风险的绝对增加都很小,因此临床重要性有限。