Lazzaro, E. C. MD*; Mallick, Adnan MD*; Singh, Monika MD*; Reich, Isaac MD*; Elmann, Solly MD*; Stefanov, Dimitre G. PhD†; Lazzaro, Douglas R. MD*
Glaucoma is a group of eye diseases that causes progressive deterioration of the optic nerve with a characteristic appearance, and is often accompanied by an increase in intraocular pressure (IOP). Optic disc changes are accompanied by a typical pattern of irreversible visual field loss. Glaucoma is the world’s leading cause of irreversible blindness and the second most common cause of blindness worldwide.1 The Eye Disease Prevalence Research Group determined that primary open-angle glaucoma, the most common type of glaucoma, affected 2.22 million people in the United States in 2000. This number is expected to increase to 3.36 million by 2020, with an estimated prevalence of 1.86% in people older than 40 years.2 In addition, the prevalence among blacks is nearly 3 times that of whites, and it is the leading cause of irreversible blindness among blacks in the United States.3
Although its precise pathophysiology is not fully understood, the development of glaucoma may be influenced by IOP,3–6 perfusion pressure,4 genetic and racial factors,3 refractive error,5 and intracranial pressure.6 Current means of management rely primarily on lowering IOP. Some IOP-lowering therapies may not be ideal for all patients because of side effects, affordability, or ease of use. This study explores an additional approach to lowering IOP.
Previous research has investigated the effect of positional changes on IOP in both glaucoma and nonglaucoma patients, indicating an overall drop in IOP in the upright position compared with the supine position.7–17 These studies found a wide range of IOP change between the upright and supine position, ranging between 1.6 and 8.6 mm Hg. Magnitude of IOP change varied according to the degree of tilt and duration of time spent in the various positions. Furthermore, results from several of these studies agree that eyes with glaucoma are more likely to experience IOP fluctuations when changing positions when compared with nonglaucomatous eyes.10,12,16 Decline in IOP in the upright position is likely a result of decreased episcleral venous pressure.18,19
Positional IOP fluctuations may not be detected by ophthalmologists during clinic visits. Hours spent in the supine position while sleeping may be increasing the progression of optic nerve loss in patients with glaucoma. Furthermore, patients at risk for glaucoma may be experiencing IOP elevations during sleep. Although ample data are available supporting supine IOP elevation, a proposal to have patients sleep in the head-elevated position has not been suggested until recently. Buys et al20 studied the effect of sleeping in a head-up position in glaucoma patients with new disc hemorrhages. During the sleep period, the mean IOP was 3.2 mm Hg lower in the 30-degree head-up position when compared with the head flat position.20 Buys and colleague’s study was groundbreaking; however, it only used a sample size of 17 patients and did not include a control group. Only glaucoma patients with new disc hemorrhages were included in the study. To our knowledge, there are no comparative data available analyzing nocturnal IOP changes when sleeping in the head-up position in glaucoma and nonglaucoma patients. Because supine IOP elevations are documented in both glaucoma and nonglaucoma patients, we designed this study to determine the postural IOP response in both groups of patients during the nocturnal supine position. We used a commercially available wedge pillow, with a 20-degree head-up angle. We chose a 20-degree pillow in our study to provide patient comfort, compliance, and ease of availability.
MATERIALS AND METHODS
The study was conducted at Kings County Hospital Center, and was approved by the Institutional Review Board of SUNY Downstate Medical Center and Kings County Hospital Center. Patients were recruited from various ambulatory care clinics, with a total of 30 patients subdivided into groups with and without glaucoma (see Table 1 for patient demographics). Patients were grouped based on self-reported disease status, and questioned whether a health care professional had ever diagnosed them with glaucoma. Patients were then recalled to the eye clinic at a later date to undergo complete eye examination to ensure proper grouping. Patients with glaucoma managed with one or more medications were included in the glaucoma group. Patients who were pregnant, unable to lie flat, diagnosed with angle closure glaucoma, or diagnosed with any disease of the cornea were excluded from the study. Details of the study were explained to each participant and written consent was obtained before participation in the study.
Each participant was required to spend 2 nonconsecutive nights at the University Hospital of Brooklyn, Sleep Disorders Center. During the first night, participants slept in the supine (flat) position without using a pillow. During the second night, participants slept with their head and upper torso at a 20-degree angle, using a wedge-shaped pillow, dimensions 8 “high×22” long. Baseline IOP was measured at 10 pm immediately after lying down while participants were still awake. Participants were then left in a dark, quiet room and encouraged to sleep on a full-sized bed. Throughout the course of the night, patients were gently awakened and IOP was measured at 2-hour intervals during the sleep period, at 12, 2, 4, and 6 am. A Tonopen Avia (Reichert Technologies Inc., Buffalo, NY) was used to measure the IOPs. The Tonopen was calibrated in accordance with the Tonopen Avia manual.
For each time interval, the IOP was recorded as the average of 3 consecutive measurements. IOP was averaged over both eyes at each measurement. Baseline IOP levels were compared using a paired t test. The main outcome was the mean IOP, averaged over the sleeping period (times 12, 2, 4, and 6 am).
Data were analyzed using a linear mixed model to account for the correlation between observations from the same individual. We used fixed effects for position and glaucoma status, and a random effect for subject. To determine if the effect of sleeping at a 20-degree angle differed between the patient groups, we tested the interaction term of glaucoma status by position. A sample size calculation determined that 19 subjects would be required to detect a difference with effect size of 0.7, with a power of 80%, and a significance level of 0.05. All P values were 2-sided; P<0.05 was considered statistically significant. An effect size of 0.7 was considered clinically significant for the entire group, as it was in the Buys and colleague’ paper. SAS version 9.2 (SAS Institute Inc., Cary, NC) was used for all analyses.
All 30 patients completed the 2-night study. There were 13 female and 17 male patients with a mean age of 54.1±6.4 years (mean±SD). There were 15 African American, 4 Asian, and 11 white patients. All 30 patients were recalled to the eye clinic to confirm self-reported glaucoma diagnoses. All 15 of the patients with self-reported glaucoma were confirmed to have glaucoma, and all 15 of the patients with self-reported absence of glaucoma were confirmed not to have glaucoma. None of the 30 patients had any evidence of angle closure or corneal pathology on examination.
Of the 15 glaucoma patients, 11 were shown to have primary open-angle glaucoma, whereas 4 were shown to have normal tension glaucoma. Glaucoma patients were on average 2 medications (see Table 2 for further information on medication regimen). Of the glaucoma patients, 3 had undergone previous trabeculectomy and 5 had undergone previous laser trabeculoplasty.
The mean IOP during the baseline awake period (10 pm) was 13.23 mm Hg±1.61 (mean±SD) in the 20-degree position compared with 13.86 mm Hg±1.87 in the flat position (P<0.001). There were no significant differences in IOP at baseline between the supine and the 20-degree head-up position (P=0.55) (Table 3). Our statement of a nonsignificant difference is supported by the narrow confidence interval (95% CI, −0.99 to 1.16) between the IOP positional changes.
The mean IOP during the sleep period was 14.50 mm Hg±1.36 (mean±SD) in the 20-degree position compared with 16.02 mm Hg±1.65 in the flat position (P<0.001). Average IOP during the sleep period was 1.51 mm Hg (95% CI, 0.99 to 2.04 mm Hg) lower in the 20-degree position compared with the flat position. This effect was not significantly different between glaucoma patients and controls (P=0.88), with an average drop of 1.56 and 1.47 mm Hg in glaucoma patients and nonglaucoma patients, respectively (Table 4).
Twenty-five of 30 patients (83.3%) had lower IOP in the 20-degree head-up position (Fig. 1). Of the 5 patients who did not show IOP reduction in the head-up position, 3 were glaucoma patients and 2 were nonglaucoma patients. The average IOP reduction in the 20-degree position was 9.33%±9.39% in glaucoma patients and 8.67%±7.08% in nonglaucoma patients (Fig. 2). IOP reduction was >10% for 11 of 30 patients overall (36.7%).
Numerous studies report IOP elevation in the supine position when compared with the head-up position.7–17 IOP elevations are associated with progressive optic disc damage, which may lead to irreversible visual field deterioration.21 Although mechanisms for supine IOP elevation are not completely understood, studies have proposed episcleral venous pressure elevation to play a role.19,22 Other theories indicate choroidal vascular engorgement to be a contributing factor, triggered by redistribution of body fluids secondary to positional change.23 Hours spent in the supine position during sleep may induce IOP elevations unknown to patients and clinicians, possibly worsening the progression of optic nerve damage. We hypothesized that patients with and without glaucoma would experience postural IOP variations during the sleep period, with a greater magnitude of change seen in glaucoma patients.
Out initial measurement at baseline (10 pm) showed no difference in IOP between the supine and 20-degree head-up position while patients were awake. Our results differ from others documenting elevations in IOP in the supine position.7–17 This may be because our baseline measurements were taken immediately after patients assumed their respective positions. Previous studies waited a period of time before measuring patient IOP.24 Furthermore, the 20-degree tilt used in our study was lower than other studies, which measured IOP at up to 90 degrees of change.7–17 Studies indicate that the magnitude of IOP change may vary according to the degree of tilt and duration of time spent in various positions.7,8,24 Further research is needed to determine what amount of time may be associated with positional changes in IOP.
Although supine elevations in IOP are well documented,7–17 few studies have investigated this phenomenon during the nocturnal period. Buys et al20 studied the effect of sleeping in a head-up position on IOP in patients with glaucoma. Patients at a 30-degree angle saw a mean IOP drop of 3.2 mm Hg during the sleep period. Over 90% of patients in his study experienced a decrease in IOP when sleeping at the 30-degree angle. Although Buys and colleagues’ and our study were designed similarly, patients in our study saw an average IOP drop of only 1.51 mm Hg when sleeping at an incline. A possible explanation for this difference is the angle at which the patients slept. Reduction of head tilt reduces the vertical head to heart distance in patients, and inversely may cause an increase in the IOP.25 Although the exact head to heart distance was not calculated in this case, previous studies document an increase in the head to heart distance as the degree of tilt increases from a supine postion,25 possibly explaining the difference in IOP variation between our study and Buys and colleagues’. Previous studies also document a varying magnitude of IOP elevation according to the angle of tilt8,24; the smaller IOP variation in our study may be a result of using a wedge pillow with a 20-degree angle as opposed to a 30-degree angle.
Positional variations of IOP can also be influenced by the presence of glaucoma. Results from most studies indicate the degree of IOP elevation in the supine position to be greater in patients with glaucoma when compared with normal healthy subjects.10,12,16 To our knowledge, our study is the first to report the effect of sleeping in the head-up position on IOP in patients with glaucoma compared with those without glaucoma.
When comparing glaucoma eyes to nonglaucomatous eyes, Jain et al10 saw a significantly greater variation in positional IOP in glaucoma patients (4.1 vs. 2.7 mm Hg). Similar results were found by Krieglstein et al19 and Hirooka et al9 where they also reported that eyes with more advanced damage had greater IOP variations. Greater variations in IOP may be due to faulty autoregulation of ophthalmic artery blood flow during postural change in glaucoma patients.10,12 Our results differ from past studies, with no significant difference in IOP reduction observed in glaucoma patients when compared with patients without glaucoma (1.56 vs. 1.47 mm Hg, P=0.88). It is important to note that several studies investigating positional IOP change have performed measurements in a fixed sequence with only minutes spent between changes in position.26 Measurement sequences and duration of time spent in various positions may be confounding factors.26 Furthermore, Gaton et al27 reported decreased IOP values on repeated measurements over time in glaucoma patients. Our study repeated IOP measurement in a fixed position over 8 hours; therefore measurements were less likely to be confounded by recent changes in position.
IOP control remains the major means of management in glaucoma patients, and even small mean IOP reductions could decrease disease progression. Postural changes may play a greater role in IOP fluctuation for certain patients, based on glaucoma status, systemic disease, and age, among several factors.9,10,12,16 Posture-induced IOP elevations may be especially difficult to control because a number of eye drops (timolol, latanoprost, or brinzolamide) may be less effective in controlling IOP during the nocturnal period.28–30 Furthermore, surgical procedures such as trabeculectomy and argon laser trabeculoplasty have been shown to have minimal response to postural-induced IOP response.15,31
In conclusion, sleeping in the 20-degree head-up position results in a lower average IOP compared with the supine position. Sleeping in the head-up position may prove to be an effective, inexpensive, and noninvasive adjunct in IOP reduction for glaucoma care. Patients spend close to one third of their lives asleep, translating into several years of increased IOP. Although sleeping vertically may perhaps prove to be beneficial for glaucoma patients, it would be a major and likely difficult adjustment for many patients to make. However, if sleeping at a more practical 20-degree angle could decrease the IOP by almost 10%, it may be of therapeutic benefit to recommend. Noting that IOP reductions were similar in nonglaucoma patients, sleeping in the head-up position could theoretically prevent or delay the onset of glaucoma in patients at risk.
Further research is needed to determine the optimal head position to provide greatest decreases in IOP while maintaining patient comfort during the sleep period. Postural changes have been used for decades as adjunctive therapy in the management of several different diseases, including congestive heart failure and gastroesophageal reflux disease. Manipulation of body position in the management of glaucoma is an idea which merits consideration. Although decreased IOP measurements are seen when sleeping in the head-elevated position, further studies are still required to investigate whether if employed consistently over a period of time, the progression of disc damage and visual field deterioration could be altered.
Our study has several limitations. The study only includes 30 patients with self-reported disease status. Patients were grouped based on subjective response to questions regarding physician-diagnosed medical conditions. Studies indicate that >50% of glaucoma patients may be unaware of their condition.32 Furthermore, the African American population, which makes up 50% of our study group, has a greater likelihood of being underdiagnosed with glaucoma.33 Because of the possibility of false diagnosis, patients were recalled to the eye clinic to confirm diagnoses.
Although our study focuses only on IOP data, numerous factors may potentially contribute to positional changes in IOP. Williams et al34 suggested that patients with systemic vascular disease may experience greater position-induced variations in IOP; patients with hypertension and diabetes showed a 2-fold greater postural IOP response when compared with normal patients. Position-induced changes of IOP and mean arterial pressure may also be far greater in patients with autonomic failure.35 Future studies may benefit by screening patients for systemic disease and recording blood pressure measurements throughout the course of the night. Other factors that may affect the magnitude of postural IOP change include intracranial pressure, scleral rigidity, refractive error, and axial length.36,37 Although the effects of these factors are incompletely understood, future studies could take them into account when investigating positional changes in IOP. Furthermore, our study included glaucoma patients with and without surgical trabeculectomy and argon laser trabeculoplasty. Although these procedures are shown to have minimal response to postural-induced IOP change,15,31 there is evidence of nocturnal IOP reduction with both surgical trabeculotomy38 and laser trabeculoplasty.39 Inclusion of these patients may have possibly blunted results. Future studies may investigate if these procedures have any effect in nocturnal posture-induced IOP change by separating patients with these procedures into a different group. It should also be taken into account that the head-up position has been associated with decreases in intracranial pressure,36 and low intracranial pressure may play a role in the development of glaucoma.6 Therefore, it is possible that the head-up sleeping position may not be beneficial to all glaucoma patients. In conclusion, there is still much further research necessary in this field to determine the pathophysiology that the head-up sleeping position plays on IOP and what other factors may affect this relationship.
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