Purpose
To investigate whether selective serotonin reuptake inhibitor use is associated with an increased risk of cataract surgery.
Design
Population-based case-control study.
Methods
setting : Olmsted County, Minnesota. patient population : Eligible patients were county residents in the Rochester Epidemiology Project. Cases included 6024 county residents aged 50+ years who underwent first-eye cataract surgery between January 1, 2004 and December 31, 2011. Controls included 6024 residents who never had cataract surgery and were matched to cases by age, sex, and date of surgery. Logistic regression models were used to compute odds ratios for differences in selective serotonin reuptake inhibitor use between cases and controls, and to adjust for confounding variables. observation procedure : Rochester Epidemiology Project databases were used to assess cataract surgery and selective serotonin reuptake inhibitor treatment. main outcome measure : Selective serotonin reuptake inhibitor use.
Results
In the cataract surgery cohort of 6024 residents, 1024 (17%) were selective serotonin reuptake inhibitor users compared to 788 (13%) in the matched cohort of 6024 residents never having cataract surgery ( P < .001). Selective serotonin reuptake inhibitor use of 1 or more years was associated with an increased risk of cataract surgery (odds ratio [OR] = 1.36; 95% confidence interval [CI], 1.23–1.51; P < .001). The associations were similar in women (OR = 1.37; 95% CI, 1.22–1.55; P < .001) and men (OR = 1.34; 95% CI, 1.12–1.61; P = .002). The risk of cataract surgery was highest with citalopram use (OR = 1.53; 95% CI, 1.33–1.77; P < .001).
Conclusion
Selective serotonin reuptake inhibitor use of 1 or more years in people aged 50+ years is associated with an increased risk of cataract surgery.
Cataract surgery rates in the United States have increased at least 2.5-fold over the last 20 years, and similar increases have been reported in other developed countries throughout the world. Additionally, cataract surgery rates have increased at a rate faster than can be explained by aging demographics alone, and the rate of increase has accelerated for women.
Many prescription drugs have been associated with cataract formation, including oral and inhaled corticosteroids, statins, and β-blockers. Recently, a population-based Canadian study suggested an association between the use of selective serotonin reuptake inhibitors and the diagnosis of cataract. Although the role of serotonin in lens metabolism is unclear, serotonin receptors have been identified in the crystalline lens of animal models, and increased serotonin levels have been shown to cause lens opacities in rats.
It is estimated that 1 in 4 women over the age of 50 years, and approximately 10% of all US residents, receive an antidepressant, mainly selective serotonin reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors. Given the increasing use of antidepressant medications in the last decade, an association between selective serotonin reuptake inhibitor use and an increased risk of cataract surgery would be useful information and warrants further evaluation. Therefore, the purpose of our population-based case-control study was to investigate an association between selective serotonin reuptake inhibitor use and incident cases of first-eye cataract surgery within a defined American population by using the resources of the Rochester Epidemiology Project (REP).
Methods
Data Sources
A population-based case control study was conducted. All aspects of the study were prospectively approved by Mayo Clinic and Olmsted Medical Center institutional review boards. Data were obtained by using the resources of the Rochester Epidemiology Project, a medical records linkage system that has linked and archived the medical records, medical diagnoses, surgical interventions, and demographic information of virtually all persons residing in Olmsted County, Minnesota (2010 total county population = 144 248). The characteristics of the Olmsted County population are very similar to Minnesota and the Upper Midwest, although compared to the entire United States, Olmsted County is less ethnically diverse, more educated, and wealthier. Virtually all of the medical care for this relatively isolated, semi-urban county is provided by the Mayo Clinic and its 2 affiliated hospitals, Olmsted Medical Center and its affiliated hospital, and the Rochester Family Medicine Clinic. Only a small proportion of the population (approximately 2%) does not allow any of their medical records to be used for research.
To enumerate the population, the medical records are linked across different health care providers to create a list of unique subjects. Then, residency criteria and imputations are applied to describe the residency status of residents over time. As a result, the Rochester Epidemiology Project provides a data-retrieval system for a complete description of virtually all sources of medical care used by the Olmsted County population over time.
Ascertainment of Cases and Controls
Cases included a population-based cataract surgery cohort of 6024 Olmsted County residents aged 50 years and older who underwent incident first-eye cataract surgery between January 1, 2004 and December 31, 2011. Cases were retrospectively identified by using the International Classification of Diseases, 9th Revision (ICD-9) procedure codes 13.1, 13.11, 13.2/9, 13.3, 13.41, 13.42, 13.43, 13.51, 13.59/9, 13.69/9, and 13.71 and Current Procedural Terminology (CPT) procedure codes 66982, 66983, or 66984 for cataract surgery. Included were first-eye cataract surgeries performed by phacoemulsification, extracapsular cataract extraction, intracapsular cataract extraction, lens aspiration, and pars plana lensectomy as a primary procedure or as a combined procedure with penetrating keratoplasty, trabeculectomy, or glaucoma shunt procedure. Pars plana lensectomy when combined with a vitreoretinal procedure to improve surgical visualization and cataract extraction in the surgical management of ocular trauma were excluded. A previous REP manual record review of the codes used to identify cases verified case over-ascertainment of less than 1% when using the codes listed above.
Controls included a cohort of 6024 county residents who never had cataract surgery and who were matched to cases by sex, age (±1 year), and date of cataract surgery (±30 days). Olmsted County residence at the time of surgery was verified for cases and controls using previously validated procedures.
Drug Prescription Records
The Rochester Epidemiology Project prescription drug database captured all drug information (drug name, strength, quantity, day supply) on all outpatient drug prescriptions obtained from Mayo Clinic and Olmsted Medical Center and written for Olmsted County residents in the cases and controls between January 1, 2003 and December 31, 2011. Since 2003, both institutions have used proprietary electronic prescription systems in their office and hospital outpatient settings. Electronic prescriptions were retrieved from the proprietary systems and converted into RxNorm codes. Prescriptions were then grouped using the National Drug File – Reference Terminology (NDF-RT). Available SSRIs included citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline. Venlafaxine and duloxetine, serotonin norepinephrine reuptake inhibitors, were also assessed.
An event was defined as the identification of a selective serotonin reuptake inhibitor user and serotonin norepinephrine reuptake inhibitor user who was continuously prescribed medication for 1 year or longer before the cataract surgery date (cases) or index date (controls).
Statistical Analysis
Differences in selective serotonin reuptake inhibitor use and serotonin norepinephrine reuptake inhibitor use between cases and controls were compared by calculations using logistic regression models. The estimated odds ratios and the associated 95% confidence intervals from these models were used to summarize the relationships. The models were also used to adjust for potential confounding variables that are risk factors for cataract formation, including diabetes and oral corticosteroid use. We do not have county-specific data for smoking status or self-reported exposure to secondhand smoke and these could not be analyzed. A P value of less than .05 was considered to be statistically significant.
Results
During the study period 2004 through 2011 there were 6024 residents in the primary cataract surgery cohort (cases) and 6024 residents in the age-, sex, and date of surgery–matched cohort without cataract surgery (controls). After matching, there was no difference between cases and controls in age (74 ± 9 years) and sex (40% men, 60% women). Diabetes was present in 538 of the 6024 cases (9%), and this was significantly higher when compared to diabetes in 444 of the 6024 controls (7%; P < .001). Oral corticosteroids were used in 360 of the 6024 cases (6%), and this was significantly higher when compared to corticosteroid use in 236 of the 6024 controls (4%; P < .001).
Selective serotonin reuptake inhibitors were used by 1024 of the 6024 cases (17%) who had cataract surgery compared to 788 of the 6024 matched controls (13%) who never had cataract surgery ( P < .001; Table 1 ). Selective serotonin reuptake inhibitor use of 1 or more years was associated with an increased risk of cataract surgery (odds ratio [OR] = 1.36; 95% confidence interval [CI], 1.23–1.51; P < .001) in residents 50+ years of age ( Table 1 ); the association was similar for women (OR = 1.37; 95% CI, 1.22–1.55; P < .001) and men (OR = 1.34; 95% CI, 1.12–1.61; P = .002; Table 2 ). Diabetes (OR = 1.23; 95% CI, 1.08–1.41; P = .002) and oral corticosteroid use (OR = 1.56; 95% CI, 1.32–1.84; P < .001) were significantly associated with an increased risk of cataract surgery. After adjusting for diabetes and oral corticosteroid use, selective serotonin reuptake inhibitor use was still associated with a higher risk of cataract surgery ( P < .001).
| Variable | Cataract Surgery, n (%) | Univariate OR (95% CI) | P Value | |
|---|---|---|---|---|
| Yes (n = 6024) | No (n = 6024) | |||
| No SSRI use | 5000 (83) | 5236 (87) | – | – |
| Any SSRI use | 1024 (17) | 788 (13) | 1.36 (1.23–1.51) | <.001 |
| Individual SSRI | ||||
| Citalopram | 486 | 326 | 1.53 (1.33–1.77) | <.001 |
| Sertraline | 283 | 225 | 1.27 (1.06–1.52) | .009 |
| Paroxetine | 173 | 142 | 1.22 (0.98–1.53) | .08 |
| Fluoxetine | 175 | 148 | 1.19 (0.95–1.48) | .13 |
| Escitalopram | 83 | 72 | 1.16 (0.84–1.59) | .37 |
| Fluvoxamine | 4 | 1 | 3.97 (0.45–35.27) | .22 |
| SSRI use | Women | Men | ||||||
|---|---|---|---|---|---|---|---|---|
| Cataract Surgery, n (%) | OR (95% CI) | P | Cataract Surgery, n (%) | OR (95% CI) | P | |||
| Yes (n = 3623) | No (n = 3623) | Yes (n = 2401) | No (n = 2401) | |||||
| No | 2893 (80) | 3061 (85) | – | – | 2175 (88) | 2107 (91) | – | – |
| Yes | 730 (20) | 562 (15) | 1.37 (1.22–1.55) | <.001 | 226 (12) | 294 (9) | 1.34 (1.12–1.61) | .002 |
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