Obstructive sleep apnea (OSA) is characterized by total or partial obstruction of the upper airway, which leads to impaired sleep, autonomic dysfunction, and transient nighttime hypoxemia [
The Taiwan National Health Insurance was a nationwide, single-payer insurance established in 1996 and covered 99% Taiwan citizen since 1998. The National Health Research Institutes involved all reimbursement claim data to establish and maintain the National Health Insurance Research Database. All personal information was encoded to protect personal privacy with surrogated identification before being released to the research.
The study used the Longitudinal Health Insurance Database which was a subset of National Health Insurance Research Database. The Longitudinal Health Insurance Database randomly selected one million individuals and was constructed of annual claim data. This claim dataset provided scramble and anonymous identification numbers to connect to the each person’s relevant claim information, including the individual’s sex and date of birth, registry of medical services, and medication prescriptions.
All of the individual’s disease history was recorded from inpatient and outpatient files and disease registry based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM).
This research was a population-based retrospective cohort study. The OSA cohort collected the newly diagnosed OSA (ICD-9-CM 780.51, 780.53, and 780.57, and with the polysomnography exam) patient in 2000–2009. Polysomnography, consisting of a simultaneous recording of multiple physiologic parameters related to sleep and wakefulness, is often considered the criterion standard for diagnosing OSA, determining the severity of the disease, and evaluating various other sleep disorders that can exist with or without OSA [
We also investigated the effect of OSA treatment to the risk of glaucoma. The OSA patients were divided into 4 groups: (1) without any treatment, (2) with surgery (pharyngeal or nasal surgery), (3) with continuous positive airway pressure (CPAP), and (4) with multiple modalities (both surgery and CPAP). The types of pharyngeal surgery included were tonsillectomy (T), adenoidectomy (A), adenotonsillectomy (T&A), uvulopalatopharyngoplasty (UPPP), and laser assisted uvuloplasty (LAUP). The nasal surgery contained septoplasty, turbinoplasty, stomatoplasty, and laser turbinoplasty.
We considered the following comorbidities as possible confounding factors. The comorbidities included hypertension (ICD-9-CM 401–405), diabetes (ICD-9-CM 250), hyperlipidemia (ICD-9-CM 272), and coronary artery disease (CAD, ICD-9-CM 410–414) from inpatient and outpatient file before index date.
The distributions of these two cohorts were showed by mean and standard deviation (SD) for age and number and proportion for sex and comorbidities. The
All data managements and statistical analyses used SAS v.9.3 (SAS Institute, Cary, NC, USA) statistical package. The curves of cumulative incidence rates were drawn by R software (R Foundation for Statistical Computing, Vienna, Austria). Statistical significance was defined as
There were 2528 individuals with OSA and 10112 individuals without OSA (comparison cohort). In Table
The results of comparing baseline demographic status and comorbidity between comparison cohort and sleep apnea syndrome (OSA) cohort.
Variable | Comparison cohort |
OSA cohort |
|
---|---|---|---|
|
| ||
Age, years (SD)* | 45.1 (14.9) | 45.1 (14.8) | 0.9233 |
Follow-up, years (SD) | |||
Without glaucoma | 4.4 (2.6) | 4.5 (2.5) | <0.0001 |
With glaucoma | 3.4 (2.6) | 3.0 (2.5) | |
Sex | >0.99 | ||
Female | 2244 (22.2) | 561 (22.2) | |
Male | 7868 (77.8) | 1967 (77.8) | |
Management for OSA | |||
Without treatment | — | 1431 (56.6) | |
With surgery only | — | 296 (11.7) | |
With CPAP only | — | 617 (24.4) | |
OSA with multiple modality | — | 184 (7.3) | |
Comorbidity | |||
Without any comorbidity | 7273 (71.9) | 1265 (50.0) | <0.0001 |
Hypertension | 1975 (19.5) | 902 (35.7) | <0.0001 |
Diabetes | 764 (7.6) | 264 (10.4) | <0.0001 |
CAD | 830 (8.2) | 498 (19.7) | <0.0001 |
Hyperlipidemia | 1433 (14.2) | 755 (29.9) | <0.0001 |
Table
Incidence rates of glaucoma and multiple Cox regression model measured hazard rates ratio between two study cohorts.
Variable | Comparison cohort | OSA cohort | Crude HR (95% CI) | Adjusted HR (95% CI) | ||||
---|---|---|---|---|---|---|---|---|
Event | PYs | Rate | Event | PYs | Rate | |||
Total | 191 | 44535 | 42.89 | 101 | 11109 | 90.91 | 2.12 (1.67–2.70) | 1.88 (1.46–2.42) |
Age group | ||||||||
0–44 | 42 | 22434 | 18.72 | 29 | 5576 | 52.01 | 2.77 (1.73–4.45) | 2.42 (1.48–3.96) |
45–54 | 54 | 11980 | 45.08 | 26 | 3019 | 86.12 | 1.90 (1.19–3.03) | 1.64 (1.00–2.68) |
≧55 | 95 | 10121 | 93.86 | 46 | 2514 | 182.95 | 1.95 (1.37–2.78) | 1.65 (1.14–2.40) |
Sex | ||||||||
Female | 44 | 9350 | 47.06 | 30 | 2309 | 129.94 | 2.75 (1.73–4.38) | 2.23 (1.37–3.65) |
Male | 147 | 35185 | 41.78 | 71 | 8801 | 80.68 | 1.93 (1.45–2.56) | 1.75 (1.30–2.35) |
Comorbidity | ||||||||
Without any comorbidity* | 84 | 32703 | 25.69 | 30 | 5671 | 52.9 | 2.06 (1.36–3.13) | 2.40 (1.58–3.66) |
Hypertension | ||||||||
No | 106 | 36464 | 29.07 | 51 | 7235 | 70.49 | 2.43 (1.74–3.39) | 2.48 (1.76–3.50) |
Yes | 85 | 8071 | 105.31 | 50 | 3875 | 129.05 | 1.22 (0.86–1.73) | 1.37 (0.96–1.97) |
Diabetes | ||||||||
No | 157 | 41504 | 37.83 | 84 | 10022 | 83.82 | 2.22 (1.70–2.89) | 1.99 (1.50–2.62) |
Yes | 34 | 3031 | 112.17 | 17 | 1087 | 156.32 | 1.34 (0.75–2.41) | 1.29 (0.70–2.38) |
CAD | ||||||||
No | 159 | 41148 | 38.64 | 68 | 8962 | 75.87 | 1.96 (1.48–2.61) | 1.96 (1.46–2.62) |
Yes | 32 | 3387 | 94.47 | 33 | 2147 | 153.7 | 1.60 (0.98–2.60) | 1.66 (1.01–2.72) |
Hyperlipidemia | ||||||||
No | 140 | 38724 | 36.15 | 60 | 7944 | 75.53 | 2.09 (1.54–2.83) | 1.95 (1.42–2.66) |
Yes | 51 | 5811 | 87.77 | 41 | 3166 | 129.51 | 1.46 (0.97–2.21) | 1.60 (1.05–2.43) |
Model adjusted for age, sex, hypertension, diabetes, CAD, and hyperlipidemia.
*Model adjusted for age and sex.
PYs: person-years; rate: incidence rate, per 10,000 person-years.
Cumulative incidence rates of glaucoma in study population.
The results of stratified analyses based on age group, sex, and comorbidity for these two cohorts were also showed in Table
The incidence rates of glaucoma in comparison cohort and OSA cohort with/without managements were shown in Table
Glaucoma incidence rates and multiple Cox regression model measured hazard rates ratio among comparison cohort and OSA cohort with different managements.
Variable | Event | PYs | Rate | Crude HR (95% CI) | Adjusted HR (95% CI) |
---|---|---|---|---|---|
Comparison cohort | 191 | 44535 | 42.89 | ref | ref |
OSA without treatment | 62 | 6018 | 103.02 | 2.41 (1.81–3.21) | 2.15 (1.60–2.88) |
OSA with surgery only | 7 | 1407 | 49.75 | 1.15 (0.54–2.45) | 1.53 (0.72–3.29) |
With pharyngeal surgery | 5 | 858 | 58.25 | 1.34 (0.55–3.27) | 1.86 (0.76–4.56) |
With nasal surgery | 2 | 549 | 36.45 | 0.84 (0.21–3.38) | 1.14 (0.28–4.62) |
OSA with CPAP only | 27 | 2712 | 99.55 | 2.34 (1.56–3.50) | 1.65 (1.09–2.49) |
OSA with multiple modality | 5 | 972 | 51.46 | 1.16 (0.48–2.82) | 1.25 (0.51–3.04) |
Model adjusted for age, sex, hypertension, diabetes, CAD, and hyperlipidemia.
PYs: person-years; rate: incidence rate, per 10,000 person-years.
Cumulative incidence rates of glaucoma in study with/without management.
This study used population-based data to examine the association between glaucoma and OSA in Taiwan. Common comorbidities possibly related to both glaucoma and OSA, including hypertension, diabetes, hyperlipidemia, and coronary artery disease, were evaluated. The result shows that OSA patients have significantly higher risks of all considered comorbidities than the comparison group. To adjust the effect of age, sex, and all comorbidities, the relative risk of glaucoma for OSA versus comparison cohort was 1.88 (adjusted HR = 1.88, 95% CI: 1.46–2.42). The exact relationship between OSA and glaucoma remains unclear, with smaller prospective studies reporting a positive association but larger retrospective cohort studies declaring no association [
Very few studies evaluated if different treatment strategies would influence the risk of glaucoma in OSA. Here we first reported that OSA patients with surgery are less associated with glaucoma. Regarding the surgery method versus glaucoma risk, pharyngeal surgery (HR = 1.86) is higher than nasal surgery (HR = 1.14). As far as we know practice parameters for surgical treatment for OSA in adults were first published in 1996 by the American Academy of Sleep Medicine (AASM) [
OSA is a common disease, affecting approximately 2% of women and 4% of men residing in western communities [
Important findings were obtained from our current result. Younger patients with OSA had greater hazard ratios than older patients with OSA in glaucoma risk than non-OSA comparison cohort. Woman with OSA had greater hazard ratios than men with OSA in glaucoma risk than non-OSA comparison cohort. Similar finding was observed in another recent study by Lin et al. [
We believe our work has some strength. First, the strength of database was a large one with good sample randomization. Second, this dataset captures data on a broad range of subjects of different sociodemographic profiles unlike some smaller studies that recruit patients from a specific region which might not represent the whole population because of an overrepresentation or underrepresentation of individuals with certain sociodemographic characteristics in that area [
OSA is associated with an increased risk of glaucoma in Taiwanese population. However, OSA patients having surgery are less associated with glaucoma and are more associated with glaucoma in female and younger age. Further research is warranted to understand why different OSA treatments may have variable risk for glaucoma.
The authors have no conflict of interests to disclose.
The authors thank ENT Dr. Hsiung-Kwang Chung for comments about the current treatment strategy for OSA in Taiwan.