The reduction of intraocular pressure (IOP) after cataract extraction has been reported since the early 1990s when phacoemulsification was performed using scleral tunnel incision. In the past two decades, numerous studies have reported on the long-term effect of clear cornea phacoemulsification on IOP in normal patients and patients with various types of glaucoma. In normal patients, IOP reduction after cataract surgery ranged from 1.3 to 2.05 mm Hg at 1-year follow-up.1–3 In primary open-angle glaucoma (POAG) patients, a slightly larger range of IOP reduction from 1.8 to 3.3 mm Hg at 3 years after cataract surgery has been reported.3–6 Patients with pseudoexfoliation glaucoma also experienced a similar IOP reduction 1 year after cataract surgery.7 Cataract extraction produces the greatest IOP reduction in patients with angle closure glaucoma. The two largest studies reported a mean of 5.5 mm Hg IOP reduction at 1-year follow-up in Chinese patients and a mean of 7.2 mm Hg IOP reduction at 2-year follow-up in Japanese patients.4,8
Various factors have been found to be associated with postoperative IOP reduction. Most of these studies are in patients without glaucoma. Preoperative anterior chamber depth is one factor that has been well studied. Issa et al.9 reported preoperative anterior chamber depth to be inversely related to the reduction in postoperative IOP in nonglaucomatous patients. However, two recent prospective studies reported that preoperative anterior chamber depth or postoperative anterior chamber deepening was not associated with postoperative IOP reduction in nonglaucomatous patients.10,11 Conflicting evidence has also been reported on the associations of lens thickness and axial length with postoperative IOP reduction in nonglaucomatous patients.1,11 Preoperative IOP is the only factor consistently found to be positively correlated with postoperative IOP reduction in patients with or without glaucoma.6,7,9,12 The relationship between the preoperative factors and postoperative IOP change in POAG patients has not been well studied. The goal of this retrospective study is to identify preoperative factors that are predictive of IOP reduction after cataract surgery in elderly male patients with POAG. Cataract and POAG are two of the most common ocular conditions encountered in the large predominantly older male population treated at the Department of Veterans Affairs Medical Centers in the United States. This is the first study attempting to identify preoperative factors associated with postoperative IOP reduction in this specific population.
Institutional review board approval was obtained before initiation of the study. Charts of patients with POAG who underwent uncomplicated cataract surgery at the San Francisco Department of Veterans Affairs Medical Center with clear cornea incision and extracapsular phacoemulsification technique from the years 2001 to 2008 were reviewed. All surgeries were performed by ophthalmology residents supervised by the same two attending ophthalmologists. All of the POAG patients were treated with topical medications, with no history of laser or filtration surgery. Demographic information such as age, sex, and ethnicity were collected. Seventy-five patients were found to meet the inclusion criteria. All patients were male except for one female patient. The mean age of the patients was 78 ± 6.4 years. Most patients were self-identified as white (73%), followed by black (20%), and other ethnicities (7%). Patient demographic data are summarized in Table 1. The most common systemic conditions in this population included hypertension, type 2 diabetes, coronary artery disease, and benign prostate hypertrophy. Preoperative data collected included IOP, number and types of glaucoma medications, spherical equivalent refractive errors, central corneal thickness, anterior chamber depth, and axial length. Biometric parameters were measured by a Zeiss Humphrey IOL Master (Zeiss Meditech, Dublin, Calif). The postoperative care protocol included follow-up visits 1 day, 1 week, 1 month, 3 months, and 1 year after cataract surgery. Many patients were lost to the 1-year follow-up visit. Intraocular pressures measured 1 month or earlier after cataract surgery were not used in the study because some patients still had residual postoperative inflammation on slow tapering of topical anti-inflammatory medications. Therefore, IOP measured at the fourth postoperative visit was used for this study. Because of the retrospective nature of the study, the timing of this fourth follow-up visit was not uniform. All patients included in this study returned for the fourth follow-up visit within 3 to 6 months after surgery. Studies have shown that reduced IOP measured as early as 1 month after surgery was stable for up to 2 years in patients with and without glaucoma.1,2,4 Reduced IOP measured within 1 to 6 months after cataract surgery has also been shown to be sustained for up to 3 years in patients in the observation group of the Ocular Hypertension Treatment Study.13 These studies suggest that IOP measured 3 to 6 months after cataract surgery is representative of those measured in later postoperative periods. All postoperative notes were carefully reviewed to ensure that the patients did not have any persistent postoperative inflammation and were on only topical glaucoma medications. Exclusion criteria included patients who had any intraoperative or postoperative complications such as capsular rupture, vitreous loss, anterior chamber intraocular lens placement, postoperative endophthalmitis, and cystoid macular edema. Patients who had previous laser trabeculoplasty, filtering surgery, or other intraocular surgeries were excluded. Patients with a history of uveitis or neovascular retinal diseases were also excluded. Data from both eyes of one patient were collected if available. A two-tailed paired-sample t test was used to compare preoperative and postoperative IOP. Linear mixed-effects regression models were fitted to the data, taking into account the nonindependence of the two eyes from a given patient. A p < 0.05 was considered statistically significant. Data analyses were conducted using a commercially available statistical package (lme4, R version 2.12 for MacIntosh, R Foundation for Statistical Computing, Vienna, Austria).
This article represents clinical research performed as part of the primary author’s 1 year of residency training. The original research plan included a group of POAG patients and a control group of patients without glaucoma. However, the application for institutional review board approval took 6 months. The primary author was unable to collect data for the control group because of the time constraint.
Data from 103 eyes of 75 patients were collected for this study. The mean preoperative IOP was 15.2 ± 3.3 mm Hg (range, 9.0 to 24.0 mm Hg). The mean postoperative IOP 3 to 6 months after cataract surgery was 13.4 ± 2.5 mm Hg (range, 9.0 to 21.0 mm Hg). There was a statistically significant mean postoperative IOP reduction of 1.8 ± 3.5 mm Hg (p < 0.001). Most eyes (76 [74%] of 103) had decreased IOP after cataract surgery. Eight percent of eyes (8 of 103) had no change in their IOP after cataract surgery. A significant number of eyes (19 [18%] of 103) had increased IOP after cataract surgery. The mean preoperative and postoperative IOPs for each of the three groups of patients are presented in Table 2. The mean preoperative IOPs for eyes with increased, same, and decreased postoperative IOPs were 12 ± 2.2 mm Hg, 14.0 ± 2.3 mm Hg, and 16.4 ± 3.1 mm Hg, respectively. The mean postoperative IOPs change for eyes with increased and decreased postoperative IOPs were +2.7 ± 2.1 mm Hg and −3.7 ± 2.5 mm Hg, respectively. Eyes with decreased postoperative IOPs had significantly higher preoperative IOPs than eyes with the same or increased postoperative IOPs (p < 0.01).
The mean number (1.5 ± 1.3) and class of glaucoma medications used before and after cataract surgery remained unchanged. Preoperative IOP was the only factor found to have a significant association with postoperative IOP reduction. Higher preoperative IOPs were strongly associated with greater postoperative IOP reductions (p < 0.001). Preoperative factors and their association with postoperative IOP reduction are presented in Table 3. Spherical equivalent refractive errors, central corneal thickness, axial length, and anterior chamber depth were not significantly associated with postoperative IOP reductions. Linear regression analysis showed a moderate correlation between preoperative and postoperative IOPs (Fig. 1). The Pearson correlation coefficient and R 2 values are 0.33 and 0.11. The relationship between preoperative IOP and postoperative IOP change is demonstrated by Fig. 2.
The amount of IOP reduction (1.8 ± 3.5 mm Hg) after cataract surgery in our study population is within the range of postoperative IOP change previously reported in POAG patients. Most eyes (82%) in this study had decreased or the same postoperative IOPs after cataract surgery. Interestingly, 18% of eyes had increased postoperative IOPs. This group of eyes with increased postoperative IOPs had significantly lower mean preoperative IOPs than eyes with the same or decreased postoperative IOPs. The mean preoperative IOP for eyes with increased postoperative IOPs was 12.2 ± 2.2 mm Hg. It seems that POAG eyes with preoperative IOPs in the low teens tend to have increased postoperative IOPs. This finding has not been previously mentioned in other studies on this topic. The reason why POAG eyes with low preoperative IOPs tended to have increased postoperative IOPs is unclear. The number of eyes in this group was too small to achieve statistical power in the analysis of which preoperative factors are associated with the increased postoperative IOPs.
Preoperative IOP was the only preoperative factor significantly associated with postoperative IOP reduction in this group of POAG patients from a Veterans Affairs medical center. All of the other preoperative factors, including anterior chamber depth, axial length, central corneal thickness, and spherical refractive error, were not associated with postoperative IOP reduction. Eyes with higher preoperative IOPs experience greater IOP reductions after phacoemulsification cataract extraction. This relation is even stronger in patients with ocular hypertension preoperatively. Patients in the observation group of the Ocular Hypertension Treatment Study who underwent cataract extraction had a postoperative IOP reduction proportional to their preoperative IOP. Those patients with preoperative IOP in the highest tertile (>25 mm Hg) experienced on average 22.5% reduction in postoperative IOP.13
The mean number of glaucoma medications used in this study population did not change before and after cataract surgery despite many patients having a significant IOP reduction. Because of the retrospective nature of this study, the clinical decision-making process that leads to maintenance of therapy cannot be deduced. A previously published prospective study reported an average reduction of 0.6 and 1.2 medications in open-angle glaucoma patients and angle closure glaucoma patients, respectively, after cataract surgery.4
One proposed explanation for the reduced IOP is that the aqueous outflow facility is increased after cataract surgery in patients with reduced preoperative outflow facility.14 The mechanism responsible for the increased outflow facility and IOP reduction after cataract surgery is not well understood. The most popular proposed mechanism attributes the IOP reduction to the widening of the anterior chamber angle. On average, the anterior chamber angle widens by 17 degrees in eyes with angle closure glaucoma and 10 degrees in eyes with open-angle glaucoma.15 It has been reported that nonglaucomatous eyes with open angles also experienced 13 degrees of anterior chamber angle widening after cataract surgery.16 A recent prospective study in nonglaucomatous eyes by Huang et al.11 found that each 0.1-mm increase in angle opening distance corresponded to 0.47 mm Hg and 0.32 mm Hg decrease in IOP after cataract surgery in eyes with narrow angles and open angles, respectively. Eyes with narrow angles or angle closure glaucoma experience the greatest angle widening and reduction of IOP after cataract surgery. Phacoemulsification alone has been found to result in greater angle widening than combined phaco-trabeculectomy even in eyes with significant synechial closure.8 The removal of the thickened lens relieves pupillary block and apposition of peripheral iris to the trabecular meshwork (TM), resulting in improved aqueous drainage in eyes with narrow angles or angle closure glaucoma. However, the relationship between postoperative angle widening and IOP reduction is not as intuitive in patients with POAG whose anterior chamber angles are not obstructed. Some authors propose that extraction of the lens allows the anterior lens capsule to resume a more posterior location, resulting in zonular traction on the ciliary body and scleral spur. The posterior traction on the ciliary body and scleral spur expands the lumen of Schlemm canal, leading to improved aqueous outflow.6,17 Although this proposed mechanism seems reasonable, there is not yet any anatomical study published to support this theory.
Biologic mechanisms for postoperative IOP reduction have also been proposed based on supporting evidence from in vitro studies. Studies have proposed that endogenous prostaglandin F2 released from the low-grade inflammation after phacoemulsification increased aqueous outflow.2,11,17 Recent works by Wang et al.18 suggest another biologic mechanism. They initially identified a protective signaling pathway against oxidative stress that was only active in TM cells from glaucomatous eyes. This pathway started with activation of interleukin-1 (IL-1), leading to expression of ELAM-1 (endothelial leukocyte adhesion molecule 1).18 Exogenous IL-1 had been found to increase aqueous outflow facility in rat eyes.19 This pathway was protective against stress stimulus like elevated IOP in the short-term. However, with chronic amplification, oxygen-free radicals generated as signaling intermediate could cause irreversible cell damage to the TM.
When cultured TM cells from nonglaucomatous human eyes were treated with phacoemulsification ultrasound, IL-1 and ELAM-1 were expressed and released.20 The level of IL-1 in glaucomatous TM cells was also found to be increased after phacoemulsification ultrasound but did not reach statistical significance. This was likely caused by the fact that these molecules were already constitutively produced in glaucomatous TM cells. Another biologic mechanism that increased aqueous outflow was discovered in studies of the biologic effects of selective laser trabeculoplasty (SLT). Alvarado et al.21 found that SLT induced cytokine release and recruitment of monocytes, resulting in increased permeability across human Schlemm canal endothelial cells. It is possible that cytokines released from postoperative inflammation after cataract surgery may induce similar biologic changes. Shazly et al.22 compared the level of IOP reduction after SLT in pseudophakic and phakic patients with ocular hypertension and POAG. They found that IOP reduction was significantly less in pseudophakic eyes than that in phakic eyes at 2 weeks after SLT. The level of IOP reduction from SLT in pseudophakic eyes reached similar levels as that in phakic eyes at 3 months of follow-up. The authors22 proposed that SLT and phacoemulsification may share a similar mechanism of IOP reduction involving inflammatory mediators given the delayed response to SLT in pseudophakic eyes.
The results from our retrospective study indicate that only preoperative IOP is significantly associated with postoperative IOP reduction after cataract surgery in POAG patients. A higher preoperative IOP is strongly associated with a greater postoperative IOP reduction. This finding has important implications when considering combined cataract extraction and filtration surgery for POAG patients with less than optimal IOP control. Cataract surgery alone may lead to significant IOP reduction in a selected group of POAG patients so additional surgery and the potential complications of trabeculectomy may be avoided. Clinicians should also use caution when considering POAG patients with very low preoperative IOPs for cataract surgery because these patients tend to have minimal reductions or even a mild increase in postoperative IOPs. It will be helpful to identify preoperative factors associated with postoperative IOP increase in these patients in future studies.
The mechanisms of postoperative IOP reduction are not well understood. In addition to the mechanical effect from anterior chamber angle widening, there is evidence supporting biologic pathways that increase aqueous outflow. Future studies on these biologic pathways may lead to new therapeutic targets for IOP reduction. This study is limited by its retrospective nature. The study population is limited to the elderly male population typical at Department of Veterans Affairs Medical Centers. Clinicians should be cautious in extrapolating findings from this study to other patient populations.
Miami Veterans Affairs Healthcare System
Surgical Service Ophthalmology
1201 N.W. 16th St
Miami, FL 33125
Received April 6, 2012; accepted October 16, 2012.
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