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Context: Fluoroquinolones are commonly prescribed classes of antibiotics. Despite numerous case reports of ocular toxicity, a pharmacoepidemiological study of their ocular safety, particularly retinal detachment, has not been performed.Objective: To examine the association between use of oral fluoroquinolones and the risk of developing a retinal detachment.Design, Setting, and Patients: Nested case-control study of a cohort of patients in British Columbia, Canada, who had visited an ophthalmologist between January 2000 and December 2007. Retinal detachment cases were defined as a procedure code for retinal repair surgery within 14 days of a physician service code. Ten controls were selected for each case using risk-set sampling, matching on age and the month and year of cohort entry.Main Outcome Measure: The association between retinal detachment and current, recent, or past use of an oral fluoroquinolone.Results: From a cohort of 989,591 patients, 4384 cases of retinal detachment and 43,840 controls were identified. Current use of fluoroquinolones was associated with a higher risk of developing a retinal detachment (3.3% of cases vs 0.6% of controls; adjusted rate ratio [ARR], 4.50 [95% CI, 3.56-5.70]). Neither recent use (0.3% of cases vs 0.2% of controls; ARR, 0.92 [95% CI, 0.45-1.87]) nor past use (6.6% of cases vs 6.1% of controls; ARR, 1.03 [95% CI, 0.89-1.19]) was associated with a retinal detachment. The absolute increase in the risk of a retinal detachment was 4 per 10,000 person-years (number needed to harm = 2500 computed for any use of fluoroquinolones). There was no evidence of an association between development of a retinal detachment and β-lactam antibiotics (ARR, 0.74 [95% CI, 0.35-1.57]) or short-acting β-agonists (ARR, 0.95 [95% CI, 0.68-1.33]).Conclusion: Patients taking oral fluoroquinolones were at a higher risk of developing a retinal detachment compared with nonusers, although the absolute risk for this condition was small. [ABSTRACT FROM AUTHOR]

Importance: Taxane-based chemotherapy agents, such as docetaxel and paclitaxel, are used for treating a wide range of cancers. Although much has been published on adverse events related to taxanes, data on ocular outcomes with these very important drugs are scant., Objective: To quantify the risk of 3 mutually exclusive ocular adverse events of epiphora, cystoid macular edema (CME), and optic neuropathy with taxane-based chemotherapy agents by undertaking a large pharmacoepidemiologic study., Design, Setting, and Participants: This retrospective cohort study design used a private health-claims database from the US that captures health information of more than 150 million enrollees. The study team created a cohort of new users of women with cancer who were taking taxane-based chemotherapy (docetaxel or paclitaxel) and new users of tamoxifen as controls. Study members were observed to the first incidence of each of the 3 mutually exclusive outcomes. An analysis of taxane-only users was also undertaken., Exposure: Tamoxifen (unexposed) and taxanes (ie, paclitaxel and docetaxel) as the exposed., Main Outcomes and Measures: First diagnosis of (1) epiphora, (2) cystoid macular edema (CME), or (3) optic neuropathy ascertained using International Statistical Classification of Diseases and Related Health Problems, Ninth Revision or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision., Results: Among the 18 219 users in the epiphora analysis and optic neuropathy analysis, there were 1824 taxane users (paclitaxel and docetaxel) (age, mean [SD], 62.1 [12.7] years) and 16 395 tamoxifen users (age, mean [SD], 54.6 [12.8] years), respectively. The crude hazard ratio (HR) for epiphora was 5.55 (95% CI, 2.99-10.29) and adjusted HR was 5.15 (95% CI, 2.79-9.54). For optic neuropathy, the crude HR was 4.43 (95% CI, 1.10-17.82) and the adjusted HR was 4.44 (95% CI, 1.04-18.87). Among the 18 433 users in the CME analysis, there were 1909 taxane users (paclitaxel and docetaxel) (age, mean [SD], 62.5 years) and 16 524 tamoxifen users (age, mean [SD], 54.6 years). The crude HR for CME comparing taxane users with tamoxifen users was 1.37 (95% CI, 0.72-2.60) and adjusted HR was 1.33 (95% CI, 0.70-2.53). The HRs for epiphora and CME in the taxane cohort during the time of exposure compared with the period prior to use of the drugs were 2.86 (95% CI, 1.11-7.39) and 2.27 (95% CI, 0.68-7.54), respectively., Conclusions and Relevance: In a cohort of women who were using taxane chemotherapy agents, there was an association with elevated risk for epiphora, CME, and optic neuropathy. Ophthalmologists and oncologists should be aware of these adverse events in women with breast cancer who receive these drugs.

Importance: Recent case reports suggest use of topical prostaglandin analogues (PGAs) might increase the risk of spontaneous abortions in pregnant people who take these drugs for intraocular pressure control. However, because these reports are derived mainly from voluntary adverse drug reaction databases, they might be prone to reporting bias., Objective: To examine the risk of spontaneous abortions among pregnant people who take topical PGAs., Design, Setting, and Participants: The PharMetrics Plus database (IQVIA) for health claims in the United States from 2006 to 2020 was used as the data source. The percentage of spontaneous abortions was quantified among patients aged 15 to 45 years who were pregnant and took a topical PGA medication during this period compared with a random sample of people in the database not taking a PGA agent., Main Outcomes and Measures: Diagnosis of a spontaneous abortion was ascertained through procedure codes or codes from the International Classification of Diseases, Ninth Revision, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision., Results: A total of 3881 people of reproductive age who were prescribed PGAs and 3881 control participants not taking PGAs were identified. Among the 3881 patients in the PGA cohort, 261 were pregnant and 26 had a spontaneous abortion code. Among the 26 individuals, 12 (4.6%) had a spontaneous abortion code within 90 days of the pregnancy code and had an overlapping prescription for a PGA. Among the 12 individuals, 5 (41.7%) were in the age category 40 to 45 years. In the control group, there were 801 pregnancies, 56 of which led to spontaneous abortions (7%), resulting in an increased risk of 2.4% (95% CI, -0.7% to 5.4%; P = .17)., Conclusion and Relevance: The results of this case-series study suggest no association between use of PGAs and risk of spontaneous abortions. Given the nature of this study design and potential for unmeasured confounding factors, these results could be explored further in future epidemiologic studies that can better control for potential confounding variables and more accurately ascertain spontaneous abortions through perinatal databases.

Importance: A number of case reports and small epidemiologic studies have quantified the risk of ocular adverse events associated with the use of phosphodiesterase type 5 inhibitors (PDE5Is). However, results have been conflicting, and epidemiologic data on the risk of serous retinal detachment (SRD) and retinal vascular occlusion (RVO) are not available., Objective: To quantify the risk of SRD, RVO, and ischemic optic neuropathy (ION) associated with the use of PDE5Is., Design, Setting, and Participants: This cohort study with a nested case-control analysis was performed using data obtained from the PharMetrics Plus database (IQVIA) from January 1, 2006, to December 31, 2020. Cohort members were followed up until the first diagnosis of SRD, RVO, or ION or termination of insurance coverage. For each case, 4 controls were matched by age and time of study entry using density-based sampling. Risk for regular users of PDE5Is was compared with that for nonusers, adjusting for potential confounding variables. Cases with diagnoses of SRD, RVO, and ION in the year before the cohort were excluded., Main Outcomes and Measures: First diagnosis of SRD, RVO, or ION identified by International Classification of Diseases, Ninth Revision or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes. Adjusted incidence rate ratios (IRRs) with 95% CIs were calculated using conditional logistic regression, controlling for hypertension, coronary artery disease, smoking, and diabetes (for all 3 outcomes) as well as sleep apnea for the ION outcome., Results: The cohort consisted of 213 033 men receiving PDE5Is, including sildenafil, tadalafil, vardenafil, and avanafil. The case-control analysis included a total of 1146 cases of SRD (278), RVO (628), and ION (240) and 4584 controls, and the mean (SD) age in both groups was 64.6 (13.3) years. Patients with SRD, RVO, and ION were more likely to have hypertension, diabetes, coronary artery disease, and sleep apnea. The adjusted IRR for the composite end points of any of the 3 outcomes was 1.85 (95% CI, 1.41-2.42; incidence, 15.5 cases per 10 000 person-years). The adjusted IRR for SRD, RVO, and ION as individual outcomes was 2.58 (95% CI, 1.55-4.30; incidence, 3.8 cases per 10 000 person-years), 1.44 (95% CI, 0.98-2.12; incidence, 8.5 cases per 10 000 person-years), and 2.02 (95% CI, 1.14-3.58; incidence, 3.2 cases per 10 000 person-years), respectively., Conclusions and Relevance: Findings of this cohort study suggest that regular users of PDE5Is might have an increased risk for SRD, RVO, and ION. Regular users of PDE5Is need to be cognizant of ocular adverse events associated with these drugs and alert their physicians if they experience any visual deficits.

Importance: Intravitreous injections of anti-vascular endothelial growth factor (VEGF) agents are associated with a sustained increase in intraocular pressure. This sustained elevated intraocular pressure could lead to higher rates of glaucoma surgery to lower this pressure., Objective: To determine the risk of glaucoma surgery following repeated intravitreous bevacizumab injections., Design, Setting, Participants: This nested, case-control study acquired and analyzed data from large, population-based, linked health databases supported by the British Columbia Ministry of Health in Canada. Study participants included all patients with ophthalmic issues in British Columbia, such as those of the Provincial Retinal Diseases Treatment Program, who had received intravitreous bevacizumab injections for exudative age-related macular degeneration between January 1, 2009, and December 31, 2013. Cases were identified using glaucoma surgical codes for trabeculectomy, complicated trabeculectomy, glaucoma drainage device, and cycloablative procedure. For each case, 10 controls were identified and matched for age, preexisting glaucoma, calendar time, and follow-up time. The number of intravitreous bevacizumab injections received per year-3 or fewer, 4 to 6, or 7 or more-was determined for both cases and controls. Data analysis was performed from February 23, 2016, to November 14, 2016., Main Outcomes and Measures: Risk of glaucoma surgery compared with the number of intravitreous bevacizumab injections per year in cases and controls. Rate ratios were adjusted for covariates (diabetes mellitus, myocardial infarction, stroke, and verteporfin use)., Results: Seventy-four cases of glaucoma surgery and 740 controls were identified, with a mean (SD) age of 81.3 (8.4) years for cases and 81.4 (7.9) for controls. The case group had more males than the control group (38 [51.4%] vs 272 [36.8%]). The adjusted rate ratio of glaucoma surgery among those who received 7 or more injections per year was 2.48 (95% CI, 1.25-4.93). There was a 10.3% higher number of 7 or more injections among cases compared with controls. The adjusted rate ratio for those who received 4 to 6 injections per year compared with those who received 3 or fewer was 1.65% (95% CI, 0.84-3.23)., Conclusions and Relevance: Findings from this large, pharmacoepidemiologic study suggest that 7 or more intravitreous injections of bevacizumab annually is associated with a higher risk of glaucoma surgery and that 4 to 6 injections per year show a nonstatistically significant rate ratio in the same direction.

Importance: Epidemiologic studies have shown that antidepressants may increase the risk of angle-closure glaucoma. We examined the risk of angle-closure glaucoma with bupropion hydrochloride, a unique, popular antidepressant also marketed as a smoking cessation aid., Observations: A nested case-control study was conducted using a large health claims database in the United States from January 1, 2006, to March 31, 2014. The database contained deidentified information pertaining to a cohort of 6 110 723 patients. Cases were defined according to the first coding for angle-closure glaucoma. For each case, 10 control participants were selected and matched to the cases using density-based sampling. Adjusted rate ratios were computed for bupropion, topiramate (positive control group drug), and esomeprazole (negative control group drug). The adjusted rate ratio was 1.09 (95% CI, 0.75-1.59) for bupropion and 2.59 (95% CI, 1.56-4.30) for topiramate. In a prespecified analysis of patients younger than 50 years, the adjusted rate ratio was 1.98 (95% CI, 1.02-3.84) for bupropion and 5.30 (95% CI, 2.54-11.04) for topiramate., Conclusions and Relevance: Both bupropion and topiramate are widely prescribed drugs. The risk of angle-closure glaucoma in patients younger than 50 years was twice as high in patients taking bupropion and more than 5 times higher in patients taking topiramate.

Importance: Numerous case reports have suggested that the recent use of moxifloxacin may lead to uveitis. This epidemiologic study is, to our knowledge, the first to explore the relationship between oral moxifloxacin hydrochloride use and uveitis., Observations: We conducted a case-control study within a cohort of men aged 40 to 85 years followed up from January 2001 through December 2011. All cases with a new diagnosis of uveitis were identified. For each case, 10 control subjects were matched by age, cohort entry date, and follow-up duration. For identified uveitis cases, current use of moxifloxacin, levofloxacin, or ciprofloxacin hydrochloride was compared with nonuse. Rate ratios were adjusted for potential confounding variables. We identified 13,313 uveitis cases and 133,130 corresponding controls. Compared with nonusers of fluoroquinolones, current first-time users of moxifloxacin demonstrated the highest risk for uveitis (adjusted rate ratio, 2.98 [95% CI, 1.80-4.94]). Current first-time users of ciprofloxacin (adjusted rate ratio, 1.96 [95% CI, 1.56-2.47]) showed an increased risk for uveitis, while current first-time users of levofloxacin (adjusted rate ratio, 1.26 [95% CI, 0.90-1.77]) did not show a significant association with uveitis., Conclusion and Relevance: Current use of moxifloxacin or ciprofloxacin appears to increase the risk for uveitis. A statistically significant association of current first-time use of levofloxacin with uveitis could not be identified. Levofloxacin may pose the least risk for uveitis compared with moxifloxacin and ciprofloxacin.

Objective: To examine the association between isotretinoin and the risk for inflammatory bowel disease (IBD) among women of reproductive age., Design: Nested case-control study and meta-analysis., Setting: A US health claims database., Participants: We formed a cohort of women aged 18 to 46 years who had received at least 1 oral contraceptive prescription from May 1, 2001, through December 31, 2009. The IBD cases were required to have 3 health care contacts with documentation of IBD or a single health care contact followed by use of a drug to treat IBD. Twenty controls were selected for each case using incidence-density sampling, matched on age and date of diagnosis., Main Outcome Measures: Risk ratios (RRs) were formed for incident cases of IBD associated with the use of isotretinoin. A subgroup analysis examined the risk for IBD among those diagnosed as having Crohn disease (CD) and ulcerative colitis (UC). A meta-analysis of published and unpublished studies assessing isotretinoin and IBD used a random-effects model to estimate a pooled RR., Results: In the case-control study, we identified 2159 IBD cases (1056 with UC and 1103 with CD) and matched them with 43 180 controls. Only 10 cases (0.46%) and 191 controls (0.44%) were exposed to isotretinoin. The adjusted RR for IBD was 0.99 (95% CI, 0.52-1.90). The RRs for UC and CD were 1.10 (95% CI, 0.44-2.70) and 0.91 (0.37-2.25), respectively. For the meta-analysis, the pooled RR for IBD for the 5 studies was 0.94 (95% CI, 0.65-1.36)., Conclusions: The results of this study do not suggest an increase in the risk for IBD, including UC or CD, with use of isotretinoin. Because inflammatory acne in children and adolescents carries a high psychological burden, clinicians should not be discouraged from prescribing this drug owing to a putative association with IBD.

Context: Use of hair dyes has been suggested recently as a risk factor for several types of cancer in epidemiologic studies. This alarming news and controversial declarations by scientific organizations and general media have made necessary a systematic evaluation of the epidemiologic evidence., Objective: To examine the association between personal use of hair dyes and relative risk of cancer., Data Sources: We retrieved studies published in any language by systematically searching the MEDLINE (1966-January 2005), EMBASE, LILACS, and ISI Proceedings computerized databases and by manually examining the references of the original articles, reviews, and monographs retrieved., Study Selection: We included cohort and case-control studies reporting relative risk estimates and 95% confidence intervals (CIs) (or data to calculate them) of personal hair dye use and cancer. We excluded studies that dealt with occupational exposure. We carried out separate analyses for bladder, breast, and hematopoietic cancers and cancers of other sites. Seventy-nine studies were included of 210 articles identified in the search., Data Extraction: Data were extracted independently by 2 investigators. We used a standardized questionnaire to record information on study design, sample size, type of controls, year of publication, adjustment factors, and relative risks of cancer among ever users of hair dyes. When possible, we extracted association measures on use of permanent dyes and extensive use (>200 lifetime episodes of dye use)., Data Synthesis: Study-specific relative risks were weighted by the inverse of their variance to obtain fixed- and random-effects pooled estimates. The pooled relative risk for ever users of hair dyes was 1.06 (95% CI, 0.95-1.18) for breast cancer (14 studies), 1.01 (95% CI, 0.89-1.14) for bladder cancer (10 studies), and 1.15 (95% CI, 1.05-1.27) for hematopoietic cancers (40 studies). Other cancers were examined by only 1 or 2 studies, of which the pooled or single relative risk was elevated for brain cancer, ovarian cancer, and cancer of the salivary glands. No effect was observed for use of permanent dyes or for extensive use., Conclusions: We did not find strong evidence of a marked increase in the risk of cancer among personal hair dye users. Some aspects related to hematopoietic cancer and other cancers that have shown evidence of increased risk in 1 or 2 studies should be investigated further.