Risk of Ocular Adverse Events Associated With Use of Phosphodiesterase 5 Inhibitors in Men in the US.

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.

Association of Postoperative Topical Prostaglandin Analog or Beta-Blocker Use and Incidence of Pseudophakic Cystoid Macular Edema.

PURPOSE: The purpose of this article is to determine the association of postoperative topical prostaglandin analog (PGA) or topical beta-blocker use and the incidence of pseudophakic cystoid macular edema (CME). METHODS: This was a nested case-control study. All adult patients who underwent cataract surgery between January 1, 2006 and December 31, 2016 and who were enrolled in the PharMetrics Plus database were eligible for inclusion. The association between postoperative topical PGAs (bimatoprost, latanoprost, and travoprost/travoprost-z) or beta-blocker (betaxolol, levobunolol, and timolol) use and the incidence of pseudophakic CME was assessed by conditional logistic regression. RESULTS: Five hundred eight cases and 5080 controls were included in the analyses. Incidence of pseudophakic CME was found to be statistically significantly associated with the current postoperative use of both topical PGAs [relative risk (RR), 1.86; 95% confidence interval (CI), 1.04-3.32] and topical beta-blockers (RR, 2.64; 95% CI, 1.08-6.49). Postoperative use of each of bimatoprost (RR, 2.73; 95% CI, 1.35%-5.53%) and travoprost/travoprost-z (RR, 3.16; 95% CI, 1.42-7.03) in the year before diagnosis was demonstrated to be statistically significantly associated with the incidence of pseudophakic CME. This association was not observed to be statistically significant with the postoperative use of latanoprost (RR, 1.55; 95% CI, 0.84-2.88). CONCLUSIONS: To the best of our knowledge this is the largest study that has investigated the association between postoperative topical PGA or topical beta-blocker use and the incidence of pseudophakic CME. Postoperative use of both topical PGAs and topical beta-blockers was found to be associated with the incidence of pseudophakic CME.

Association of Repeated Intravitreous Bevacizumab Injections With Risk for Glaucoma Surgery.

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.

Correlation in Severity Between Glaucoma and Erectile Dysfunction.

PURPOSE: To examine the association between open-angle glaucoma and erectile dysfunction (ED), and investigate the correlation in severity between these 2 conditions. METHODS: Cross-sectional study with patient questionnaire and retrospective chart review. A total of 167 male patients over 40 years of age who attended ophthalmology clinic visits in Vancouver, British Columbia, Canada, participated in the study by providing written consent and responding to the survey. Patients with previous radiation or surgical prostate treatment were excluded, leaving final sample sizes of 61 glaucoma patients and 67 control patients. Presence and severity of ED was determined using a validated patient questionnaire (the International Index of Erectile Function questionnaire). Presence of glaucoma was based on previous clinical diagnosis, and severity was graded based on visual field index using a 30-2 visual field test with the SITA Standard protocol. Bivariate analysis examined the presence of ED in glaucoma patients versus controls. Risk factors including dyslipidemia, diabetes, hypertension, and smoking were adjusted for using multiple logistic regression. The association between glaucoma and ED severity was assessed with correlation and scatterplot analysis. RESULTS: Glaucoma was found to be a significant risk factor for ED in our population, with an odds ratio of 2.58 (95% confidence interval, 1.15-5.83). Severity of glaucoma and ED were significantly correlated (r=0.365, P=0.007). CONCLUSIONS: Our results demonstrate that there is a positive association between the presence of ED and the diagnosis of glaucoma and a positive association between the severity of ED and the severity of glaucoma.

Risk of angle-closure glaucoma with bupropion and topiramate.

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.

The association between cataract surgery and atypical antipsychotic use: a nested case-control study.

PURPOSE: To investigate cataract risk associated with the use of atypical antipsychotics. DESIGN: Retrospective, nested case-control study. METHODS: A large health claims database (The British Columbia Ministry of Health Databases) from British Columbia, Canada, was used from January 2000 through December 2007. Cases were defined as clinically significant cataracts requiring surgery and were identified using cataract surgery procedure codes. For each case, 4 to 10 controls were selected randomly using a density-based sampling approach and were matched to cases by age and calendar time. Rate ratios were calculated for users of atypical and typical antipsychotics adjusting for known cataractogenic factors. RESULTS: One hundred sixty-two thousand five hundred one cases of cataract surgery and 650 004 controls were included. The adjusted rate ratio for current users of atypical antipsychotics was 0.84 (95% confidence interval, 0.80 to 0.89) compared with nonusers. A greater number of prescriptions filled in the year before cataract surgery compared with the median number of filled prescriptions was associated with a lower cataract surgery rate (adjusted rate ratio, 0.70; 95% confidence interval, 0.65 to 0.75) than those with fewer prescriptions filled (adjusted rate ratio, 0.85; 95% confidence interval, 0.79 to 0.91). CONCLUSIONS: A protective association between the use of atypical antipsychotics and risk of clinically significant cataracts requiring surgery was established. Potential biochemical and neurochemical mechanisms for this protective effect are discussed.

Combination therapy as initial treatment in glaucoma and suspected glaucoma.

OBJECTIVE: We hypothesize that there may be an inappropriate overuse of initial combination therapy in patients with glaucoma and in those who are glaucoma suspects. To test this hypothesis, we examined the British Columbia Population DataBase to determine the frequency of prescription of combination eye drops as initial therapy in glaucoma patients or glaucoma suspects. DESIGN: Cohort study. PARTICIPANTS: The study cohort included all those who visited an ophthalmologist's office between 2004 and 2007. Within the cohort we identified all those who were newly prescribed any ocular hypotensive eye drop. Specifically, we identified those who had been newly prescribed any ocular hypotensive eye drop within 60 days of receiving diagnoses of glaucoma, as defined by having received an international classification for disease code ICD-9 for glaucoma 365. METHODS: We used the Population Data British Columbia (POP Data BC) as the main data source for this study. POP Data BC is a provincially linkable database that captures the physician visits (including inpatient procedures); hospital admissions; demographics; and prescription drug use of 4.5 million residents of British Columbia. RESULTS: Between 2004 and 2007, the percentage of combination therapy as the first ocular hypotensive prescription rose from 12.29% to 18.63%. CONCLUSIONS: The high percentage of combination therapy as initial therapy suggests that ophthalmologists either require additional education in principles of pharmacologic therapy or are unduly influenced by their interaction with the pharmaceutical industry.

Selective serotonin reuptake inhibitors and the risk of cataracts: a nested case-control study.

OBJECTIVE: Older-generation antidepressants have been associated with increasing the risk of cataracts. Although animal studies have alluded to a potential link between selective serotonin reuptake inhibitors (SSRIs) and the development of cataracts, no large population based-study has addressed this potential association. This study sought to quantify the risk of cataracts with SSRIs by conducting a pharmacoepidemiologic study using the linked administrative databases in the province of Quebec, Canada. DESIGN: Nested case-control study. PARTICIPANTS: A cohort of subjects who had received a coronary revascularization procedure from 1995 through 2004 in the province of Quebec, Canada. METHODS: Using an administrative data set, a case-control study was conducted within a cohort of Quebec residents who had received a coronary revascularization procedure from 1995 through 2004. Cases were defined as those with the first diagnosis of a cataract diagnosed by an ophthalmologist. For each case, 10 controls were selected and matched to the cases by index date, age, and cohort entry. Crude and adjusted rate ratios (RRs) and corresponding confidence intervals (CIs) were computed for current use of SSRIs. Rate ratios were adjusted for gender, corticosteroid use, statins, high blood pressure, antihypertensives, and antidiabetics. MAIN OUTCOME MEASURES: First International Classification for Disease (Ninth Revision) code for a cataract diagnosed by an ophthalmologist. RESULTS: Eighteen thousand seven hundred eighty-four cases and 187 840 controls met our study inclusion criteria. The adjusted RR for cataracts among current users of SSRIs was 1.15 (95% CI, 1.08-1.23). The risk of cataracts was highest with fluvoxamine (RR, 1.39; 95% CI, 1.07-1.80), followed by venlafaxine (RR, 1.33; 95% CI, 1.14-1.55) and paroxetine for cataract surgery (RR, 1.23; 95% CI, 1.05-1.45). The average time to diagnosis of cataracts while on SSRI therapy was 656 days. CONCLUSIONS: A possible association was found between current exposure to SSRIs, especially fluvoxamine and venlafaxine, and a future diagnosis of cataracts. The possibility that this observation may be the result of the effect of smoking, which could not be controlled for in the study, cannot be excluded. Future studies are needed to confirm this association in other populations.