Comparison of Posture-Induced Intraocular Pressure Changes in Medically Treated and Surgically Treated Eyes With Open-Angle Glaucoma

Abstract

Purpose.: To compare the posture-induced IOP changes in medically treated eyes with those in surgically treated eyes having open-angle glaucoma (OAG) and low IOP.

Methods.: Fifty-one posttrabeculectomized OAG eyes with a cystic filtering bleb and 51 nonoperated, medically treated OAG eyes were studied. The IOP measured with a Goldmann applanation tonometer (GAT) was 12 mm Hg or less in both groups. It was measured in the sitting and lateral decubitus positions with a rebound tonometer. The IOP was measured in the upper eye 5 minutes after assuming the lateral decubitus position.

Results.: The mean (SD) IOP measured with the GAT was 9.7 (1.5) mm Hg in the trabeculectomized eyes and 9.7 (1.4) mm Hg in the medically treated eyes (P = 0.892, unpaired t-test). In the surgically treated group, the mean (SD) IOP measured with the rebound tonometer was 10.3 (2.3) mm Hg in the sitting position and 11.3 (2.8) mm Hg in the lateral decubitus position (P < 0.001, paired t-test). In the medically treated group, the mean (SD) IOP measured with the rebound tonometer was 10.8 (2.0) mm Hg in the sitting position and 14.1 (2.9) mm Hg in the lateral decubitus position (P < 0.001, paired t-test). The greater IOP increase of 3.3 mm Hg in the medically treated group compared with the 1.0 mm Hg in the surgically treated group was significant (P < 0.001, unpaired t-test).

Conclusions.: The lower posture-induced IOP change in the successfully trabeculectomized eyes indicates that trabeculectomy will not only lead to a decrease in the IOP but also lower the posture-induced IOP change.

Introduction

Fluctuations of the IOP have been reported to be associated with the progression of glaucoma. ^1,2 There are a number of factors that can cause the IOP fluctuations; of these, the posture-induced IOP changes have been shown to be closely associated with the functional and morphologic changes in glaucomatous eyes. ^3–5 The posture-induced IOP changes have also been shown to be significantly correlated with the progression of glaucomatous visual field defects. ⁶  

Trabeculectomy is a frequently used filtering surgery to treat glaucoma even in eyes with normal tension glaucoma (NTG). ^7,8 In addition to leading to a greater IOP reduction, the eyes that have undergone trabeculectomy have been reported to have less IOP fluctuation during the diurnal IOP changes ^9,10 and after water-drinking tests ^9,11,12 than medically treated glaucoma eyes. Trabeculectomy has also been shown to reduce the development of optic disc hemorrhages. ¹³ In addition, our previous study ¹⁴ showed that trabeculectomy not only reduced the IOP but also reduced the degree of posture-induced IOP changes in patients with a functioning bleb. Although some authors ^15,16 reported contrary results on the posture-induced IOP changes after the filtering surgery, more recent articles ^17,18 support our results. Nevertheless, some investigators may suggest that the posture-induced IOP decrease after trabeculectomy was mainly due to the ability of trabeculectomy to lower the IOP. ^18,19 Because of the contradictory conclusions, we conducted a study that compared the posture-induced IOP changes between eyes that had undergone successful trabeculectomy (i.e., they had a thin-walled, cystic filtering bleb) with those of medically treated glaucomatous eyes. 

Methods

We studied 51 nonoperated, medically treated open-angle glaucoma (OAG) eyes and 51 surgically treated OAG eyes that had undergone trabeculectomy with mitomycin C. The age, sex, and IOPs obtained with a Goldmann applanation tonometer (GAT) were matched between the two groups. The IOP measured by the GAT was set at 12 mm Hg or less in both groups because of a comparatively high success rate of IOP of 12 mm Hg or less following trabeculectomy. ²⁰ This study was conducted between May 2008 and June 2013. The procedures used were approved by the institutional review board of Gifu University Graduate School of Medicine. All patients were fully informed on the procedures and signed a written consent form to participate. The procedures used conformed to the tenets of the Declaration of Helsinki. 

The ocular diagnostic examinations included the following: (1) measurements of the best-corrected visual acuity, (2) slitlamp examination, (3) central corneal thickness (CCT) measurements by ultrasonic pachymetry (SP-100 Handy Pachymeter; Tomey, Nagoya, Japan), (4) axial length measurements by an A-scan biometer (AL-1000; Tomey), (5) IOP measurements by a GAT (Haag-Streit AG, Köniz, Switzerland) and by an Icare rebound tonometer (Icare Finland Oy, Helsinki, Finland), (6) ophthalmoscopy, and (7) evaluation of the structure and width of the anterior chamber angle with a Goldmann two-mirror gonioscopic lens. Perimetry with a Humphrey Field Analyzer (Humphrey Instruments, San Leandro, CA) using the central 30-2 program was also performed. 

A diagnosis of OAG was made based on the following criteria: (1) both eyes had a gonioscopically wide open angle, (2) at least one eye had characteristic visual field defects that corresponded to the location of the glaucomatous disc excavation, ²¹ and (3) neuroradiologic, rhinologic, and general medical examinations did not disclose any pathologic conditions responsible for the optic nerve damage. Glaucomatous optic neuropathy was taken to be present when a visual field had three or more contiguous points reduced by greater than 5 decibels (dB), with one point reduced by greater than 10 dB below the age-specific threshold on static automated perimetry. Glaucomatous optic neuropathy was considered to be present when an optic disc had a focal or diffuse defect of the rim exceeding 10% of the disc diameter. Patients with any conditions that might induce glaucoma such as uveitis and lens exfoliation even in one eye were excluded. Also, patients were excluded if they had any corneal condition such as pterygium that would prevent reliable IOP measurements. Patients were classified as having NTG if none of the IOPs measured with the GAT exceeded 21 mm Hg in either eye based on our clinical records. Similarly, eyes were classified as having primary OAG (POAG) if an IOP with the GAT exceeded 22 mm Hg in at least one eye. 

Patients were assigned to two groups, a medically treated group and a surgically treated group. In the medically treated group, the patients had no history of any intraocular surgery, including laser therapy. In the surgically treated group, the same inclusion and exclusion criteria as the medically treated group were met except for the initial filtering surgery, a postoperative follow-up period of more than 1 month, and the absence of any ocular hypotensive agents for at least 1 month around the time of this study. In addition, cases with serious intraoperative or postoperative complications such as corneal decompensation and bleb-related endophthalmitis were excluded in the surgically treated group. All of the patients in both groups had an IOP with the GAT of 12 mm Hg or less at three consecutive visits. In the surgically treated group, none of the patients had received any ocular hypotensive agents at three consecutive visits. The eyes in the surgically treated group had a hypovascular or an avascular succulent filtering bleb, which was classified based on the Indiana Bleb Appearance Grading Scale. ²² In this bleb grading system, the following four parameters were scored: (1) height of the bleb on a scale of H0 (flat) to H3 (high), (2) extent of the bleb on a scale ranging from E0 (<1 clock hour) to E3 (>4 clock hours), (3) vascularity of the bleb on a scale of V0 (avascular) to V4 (extensive vascularity), and (4) the presence of bleb leakage on a scale of S0 (no leak) to S2 (streaming). The postoperative patients were enrolled if they had a filtering bleb with H2 or H3, E3, V0 to V2, and S0. The bleb morphology was classified by a single examiner (AS) by slitlamp examinations. 

Filtering surgery with mitomycin C was performed when an eye was found to have a progression of the visual field defects and was being treated with the maximum tolerable medications. A modification of the technique by Cairns was used for the trabeculectomy, as described in detail. ²³  

The IOP was measured with the rebound tonometer by a single experienced examiner (AS). To determine the posture-induced IOP change, the IOP was first measured in the sitting position with the rebound tonometer. Then, the patient was instructed to lie on a bed and turn to the lateral decubitus position. The head was placed on a soft pillow to avoid compression of the eyes, and the body was positioned so that the eye predetermined to be measured was located directly above the fellow eye. The body position was maintained for 5 minutes, and the IOP was measured in this position with the rebound tonometer. The examiner asked the patient to gaze straight ahead to a fixation point, and the IOP measurements were made by touching the transducer to the center of the patient's cornea. Five consecutive sets of measurements were made, with six measurements in each set. The average of each set was calculated automatically, and the averaged values were used for the statistical analyses. Within 5 minutes of finishing the above procedures, the IOP was measured in the sitting position with a GAT. Then, the CCT was measured by ultrasonic pachymetry. Finally, the axial length was measured with the A-scan biometer. 

For statistical analyses, one eye was randomly chosen if both eyes met the inclusion criteria. Paired or unpaired t-tests, χ² tests, or Fisher exact probability tests were used to compare the demographic data between the two groups and to evaluate the significance of the IOP changes. The calculated sample size was 39 patients in each group, which would provide 80% power to detect a 1.8–mm Hg posture-induced IOP difference, assuming an SD of 2.8 mm Hg. The level of significance for each comparison was set at P < 0.05. All statistical analyses were performed using SPSS software version 16.0 (SPSS Japan, Tokyo, Japan). 

Results

The demographic data of the subjects are summarized in Table 1. The mean (SD) age of the subjects was 59.0 (10.2) years in the medically treated group and 59.2 (10.5) years in the surgically treated group (P = 0.921, unpaired t-test). There were 29 men and 22 women in each group. The mean (SD) axial length was 25.21 (1.54) mm in the medically treated group and 24.86 (1.64) mm in the surgically treated group (P = 0.283, unpaired t-test). The mean (SD) CCT was 508.1 (27.9) μm in the medically treated group and 519.0 (29.8) μm in the surgically treated group (P = 0.060, unpaired t-test). The mean (SD) IOP with the GAT was 9.7 (1.4) mm Hg in the medically treated group and 9.7 (1.5) mm Hg in the surgically treated group (P = 0.892, unpaired t-test). The mean (SD) IOP at three consecutive visits before prescribing ocular hypotensive agents (i.e., without any medications) was 14.0 (2.6) mm Hg (range, 9.5–20.5 mm Hg) in the medically treated group. On the other hand, the mean (SD) IOP at three consecutive visits just before trabeculectomy (i.e., with several ocular hypotensive agents) was 17.9 (6.5) mm Hg (range, 10.3–53.0 mm Hg) in the surgically treated group. The mean (SD) follow-up period without ocular hypotensive agents after trabeculectomy was 4.7 (6.4) years (range, 1 month to 27 years; median, 1.6 years). There were four eyes with POAG and 47 eyes with NTG in the medically treated group and 31 eyes with POAG and 20 eyes with NTG in the surgically treated group (P < 0.001, Fisher exact probability test). 

Table 1

 

Demographic Characteristics of the Two Groups

Variable	Trabeculectomized Eyes, n = 51	Nonoperated, Medically Treated Eyes, n = 51	P Value
M/F	29:22	29:22	…
Age, y	59.2 (10.5) [33 to 84]	59.0 (10.2) [37 to 78]	0.921
OD/OS	26:25	20:31	0.233
POAG/NTG	31:20	4:47	<0.001
CCT, μm	519.0 (29.8) [455 to 592]	508.1 (27.9) [422 to 557]	0.060
Axial length, mm	24.86 (1.64) [21.72 to 30.94]	25.21 (1.54) [22.54 to 29.05]	0.283
IOP with the GAT, mm Hg	9.7 (1.5) [6 to 12]	9.7 (1.4) [6 to 12]	0.892
HFA central program 30-2 mean deviation, dB	−17.11 (−7.51) [−30.72 to −0.15]	−7.69 (−7.09) [−26.38 to −1.50]	<0.001
Postoperative follow-up period, y	4.7 (6.4) [0.1 to 26.7]	…	…

 Data are expressed as the mean (SD) [range]. HFA, Humphrey Field Analyzer.

The ocular hypotensive drugs being used by all of the patients are listed in Table 2. All of the medically treated patients were using several types of topical ocular hypotensive drugs. In the medically treated group, the most frequently used ocular hypotensive drug was prostaglandin analogues (44 eyes [86.3%]), followed by β-blockers (20 eyes [39.2%]) and topical carbonic anhydrase inhibitors (11 eyes [21.6%]). The numbers of topical ocular hypotensive drugs prescribed were one (22 patients), two (19 patients), three (7 patients), and four (3 patients). In the surgically treated group, none of the patients used any ocular hypotensive drugs. 

Table 2

 

Drug Information for the Two Groups

Drug Category	Trabeculectomized Eyes, n = 51	Nonoperated, Medically Treated Eyes, n = 51
Prostaglandin analogues	0	44 (86.3)
β-Blockers	0	20 (39.2)
α,β-Blockers	0	2 (3.9)
Topical carbonic anhydrase inhibitors	0	11 (21.6)
α-Blockers	0	6 (11.8)
α-Agonists	0	1 (2.0)
Pilocarpine	0	1 (2.0)
No medications	51 (100.0)	0

 Data are expressed as the number (percentage) of eyes administered antiglaucoma agents.

In the medically treated group, the mean (SD) IOP was 10.8 (2.0) mm Hg in the sitting position, and it increased significantly to 14.1 (2.9) mm Hg in the lateral decubitus position (P < 0.001, paired t-test). Similarly, in the surgically treated group, the mean (SD) IOP was 10.3 (2.3) mm Hg in the sitting position, and it increased significantly to 11.3 (2.8) mm Hg in the lateral decubitus position (P < 0.001, paired t-test). The mean (SD) change in the IOP between the two body positions was 3.3 (1.8) mm Hg (range, 0.0–7.0 mm Hg) in the medically treated group and 1.0 (1.6) mm Hg (range, −1.7 to 5.7 mm Hg) in the surgically treated group (Figure). The difference in the change in the mean posture-induced IOP between the two groups was statistically significant (P < 0.001, unpaired t-test; Figure). 

Figure

 

Scattergram of the IOP differences in medically treated eyes and trabeculectomized eyes. The difference between the IOP in the lateral decubitus position (LDP) minus the IOP in the sitting position (SP) is plotted on the ordinate. The mean (SD) IOP change between the two body positions was 3.3 (1.8) mm Hg (range, 0.0–7.0 mm Hg) in the medically treated group and 1.0 (1.6) mm Hg (range, −1.7 to 5.7 mm Hg) in the surgically treated group. The difference in the change in the mean posture-induced IOP between the two groups was significant (P < 0.001, unpaired t-test).

Discussion

It is well established that the IOP varies with body position, and the IOP measured in the sitting position is the lowest among all the body positions. ^24,25 Most of the earlier studies on posture-induced IOP changes evaluated the changes between the sitting and supine positions. Recent prospective studies in normal healthy volunteers ^26,27 and in patients with glaucoma ²⁸ found that the IOP in the lateral decubitus position was equal to or higher than that in the supine position. Accordingly, evaluations of the IOP in the lateral decubitus position could provide more important information for the management of glaucoma. 

The published results of the posture-induced changes in the IOP following trabeculectomy are contradictory. In earlier studies, Anderson and Grant ¹⁵ and Parsley et al. ¹⁶ reported that the IOP changes from the sitting to supine positions were greater following glaucoma surgery than in nonoperated, medically treated glaucomatous eyes. However, more recent studies do not support these earlier results. Hirooka et al. ¹⁷ reported that the average IOP reduction between the sitting and supine positions was 1.9 mm Hg from the baseline 3 months after trabeculectomy. Weizer et al. ¹⁸ found that the posture-induced IOP change was significantly lower in trabeculectomized eyes than in the nonoperated contralateral eyes. They also demonstrated that a decrease in bleb height, an absence of microcysts, and increased bleb vascularity were associated with greater postural IOP changes. ¹⁸ Our previous study ¹⁴ showed that trabeculectomy not only decreased the IOP but also reduced the degree of posture-induced IOP changes if patients had a cystic filtering bleb. We suggested that the contradictory results between previous and recent findings are due to the intraoperative or postoperative use of antimetabolites, including 5-fluorouracil and mitomycin C. 

Our results showed that successfully trabeculectomized eyes had less posture-induced IOP change than nonoperated, medically treated eyes; both groups had low IOPs of 12 mm Hg or less. However, there was a significant difference between the two groups in the proportions of POAG and NTG patients. Based on our earlier findings, trabeculectomy significantly reduced the mean (SD) IOP in 99 POAG eyes (11.1 [4.2] mm Hg), which was comparable to that in 50 NTG eyes (11.3 [4.5] mm Hg). ¹³ In addition, the mean (SD) baseline IOP before trabeculectomy was 19.6 (4.4) mm Hg (range, 13–41 mm Hg) in POAG eyes and 15.3 (1.5) mm Hg (range, 12–18 mm Hg) in NTG eyes, ¹³ suggesting that it is more difficult to maintain IOP even at the mid-teen level in eyes with POAG under maximum tolerable medications than in eyes with NTG. At present, it remains unclear whether the amount of posture-induced IOP changes might be influenced by the IOP level in the sitting position. Armaly and Salamoun ²⁹ found no significant relationship between the magnitude of the IOP change from the standing position to that in the supine position and the original IOP in the standing position in 38 normal eyes. On the other hand, Hetland-Eriksen ¹⁹ found that the posture-induced IOP elevation was greater in eyes with higher IOPs in the sitting position among 76 medically treated eyes with glaucoma. Tsukahara and Sasaki ³⁰ reported that the postural IOP elevation was higher in eyes with NTG than in eyes with POAG after 30 minutes in the supine position compared with the value in the sitting position. In contrast, our previous results showed that there was no significant difference in the posture-induced IOP changes from the sitting to the lateral decubitus position between patients with POAG and NTG. ³¹ In the present study, the posture-induced IOP change was 3.3 mm Hg in the nonoperated, medically treated group and 1.0 mm Hg in the surgically treated group. However, it is difficult to compare the magnitude of the posture-induced IOP changes in the different studies because of varying body positions, diseased eye definitions, inclusion criteria, races/ethnicities, IOP measurement techniques, and research methods. Earlier studies ^{3,6,15–18,30,32–35} reported that the postural IOP difference from the sitting to the supine position in nonoperated patients with glaucoma varied from 0.75 to 8.6 mm Hg (mean, 4.2 mm Hg). However, the postural IOP difference from the sitting to the lateral decubitus position in nonoperated glaucoma eyes was reported to be 3.7 to 5.4 mm Hg in the dependent eyes and 1.8 to 2.7 mm Hg in the nondependent eyes ^5,28 Despite our limited number of patients whose IOP with the GAT was 12 mm Hg or less, our value in the nonoperated, medically treated glaucoma eyes seems to be compatible with others. On the other hand, the mean postural IOP change in the surgically treated group was 1.0 mm Hg, which was much lower than previous reports except for one study. ¹⁵  

There are limitations to our study, which include the relatively small number of patients and the use of ocular hypotensive agents in most of the medically treated group. However, two studies reported that there was no significant relationship between the use of topical hypotensive agents and postural changes in the IOP in healthy volunteers (pilocarpine and phenylephrine hydrochloride) ²⁹ or in patients with NTG (latanoprost, timolol, and brizolamide). ³⁶ A second limitation was that there were no patients whose IOP was 6 mm Hg or less in the nonoperated, medically treated group. Therefore, we had to exclude some trabeculectomized patients whose IOP was less than 5 mm Hg, although they met the enrollment criteria. A third limitation was that we did not measure blood pressure, and some authors have pointed to its relevance to the posture-induced IOP changes. ^6,37,38  

In summary, our results showed that eyes that had undergone successful trabeculectomy had smaller posture-induced IOP changes compared with nonoperated, medically treated eyes. This is important because it is known that with older age the sleep position tends to increase to a lateral decubitus position, with fewer positional changes during the night and a greater amount of time spent in one body position. ³⁹ Taken together, trabeculectomy rather than medication might be indicated, especially in older patients. On the other hand, Stewart and associates ⁴⁰ reported that filtering surgery and medical therapy are equally effective in maintaining visual function in patients with chronic OAG who had similar IOPs. In addition, it seems important to evaluate the posture-induced IOP changes before and after medical or surgical intervention because of large individual variations in postural IOP differences. Further large-scale investigations are required to address these issues. 

Acknowledgments

Disclosure: A. Sawada, None; T. Yamamoto, None