Aim To evaluate anterior chamber biometric factors and intraoperative metrics associated with the intraocular pressure (IOP) reduction after phacoemulsification in non-glaucomatous pseudoexfoliative syndrome (PXS) eyes.
Method Thirty-three patients were enrolled in this prospective interventional study. Images were excluded if they had poor quality, poor perpendicularity or inability to locate sclera spurs. Anterior chamber depth (ACD), anterior chamber area (ACA), iris thickness, iris area, iris curvature, lens vault, angle opening distance (AOD500, AOD750) and trabecular iris space area (TISA500, TISA750) were measured in qualified images using the Zhongshan Angle Assessment Program and compared preoperatively and 3 months postoperatively. Cumulative dissipated energy (CDE), aspiration time and infusion fluid usage during cataract surgery were obtained from the phacoemulsification machine's metrics record. Postoperative IOP change was compared with these anatomical and intraoperative metric parameters.
Results Mean IOP was 18.1±3.4 mm Hg preoperatively and decreased by 3.3 mm Hg (18%) to 14.8±3.6 mm Hg at 3 months postoperatively (p<0.001). All angle parameters, ACD and ACA increased significantly postoperatively (p<0.001 for all) and iris curvature decreased (p<0.001). In univariate analysis, preoperative IOP (B=−0.668, p=0.002), infusion fluid usage (B=−0.040, p=0.04) and aspiration time (B=−0.045, p=0.003) were negatively associated with IOP decrease after phacoemulsification. Changes in IOP did not demonstrate significant associations with CDE measurements or anterior segment optical coherence tomography measurements, including preoperative angle, iris or anterior segment parameters. In the final multivariate regression model, preoperative IOP (B=−0.668, p=0.002) and infusion fluid usage (B=−0.041, p=0.04) were significantly associated with IOP drop and together can predict 45.1% (p=0.002) of the variability in IOP change.
Conclusions Non-glaucomatous patients with PXS experience moderate IOP reduction following phacoemulsification, and this effect is correlated with preoperative IOP, aspiration time and infusion fluid used intraoperatively.
- Intraocular pressure
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Pseudoexfoliation syndrome (PXS) is a systemic disorder in which a fibrillar substance is produced and deposited within ocular tissues, including the trabecular meshwork (TM). Although the incidence of PXS differs between regions and ethnic populations worldwide, it is considered the most common cause of secondary glaucoma worldwide and the most frequent cause of unilateral glaucoma.1 ,2
Approximately 25% of people with PXS develop elevated intraocular pressure (IOP) with or without glaucomatous damage. Compared with primary open angle glaucoma (POAG), there is a higher frequency and severity of optic neuropathy, worse visual field damage, worse response to glaucoma drops, more rapid progression, more severe clinical course and more frequent necessity for surgical intervention.1–4
IOP is the primary treatable risk factor for glaucoma. Determining the magnitude of IOP reduction after cataract surgery and its predictors would be valuable in aiding the clinician's decision of whether to perform cataract surgery, incisional glaucoma surgery or a combined procedure.5–9
Several reports using modern cataract surgery have shown significant short-term and mid-term reduction in IOP in patients with ocular hypertension (OHT) and glaucoma.7–16 In a recent report by the American Academy of Ophthalmology, cataract surgery results in small, moderate and marked reductions of IOP and medications for patients with POAG, pseudoexfoliation glaucoma and primary angle closure glaucoma (PACG), respectively.5
In most studies on eyes with OHT or glaucoma, the only established predictor of IOP change after phacoemulsification is the preoperative IOP.5–10 ,12–18 However, preoperative anterior chamber depth (ACD),19 angle width,12 and lens parameters20 have also been shown to be associated with IOP response after cataract surgery in some studies.
In PXS eyes, Damji et al6 reported that a greater volume of irrigation during phacoemulsification was associated significantly with a greater IOP reduction. They suggested that one or more of the following factors may be responsible for this finding: (1) washing out of exfoliation material and pigment from the anterior segment; (2) deepening of the anterior chamber angle and (3) ultrasound energy and low grade inflammation leading to enhanced aqueous outflow.
Anterior segment optical coherence tomography (ASOCT) is a non-contact method of capturing high-resolution, tomographic, cross-sectional images of anterior segment structures. It provides qualitative and quantitative assessment of the anterior segment structures that is useful for evaluation of treatment success.21 Modern phacoemulsification machines provide records of the different intraoperative metrics, including infusion fluid usage, aspiration time and cumulative dissipated energy (CDE). CDE is an estimation of the ultrasound energy applied within the eye.
The purpose of this study was to investigate the association between different angle and anterior segment parameters, ultrasound energy (expressed as CDE), irrigation volume, aspiration time and IOP response after uncomplicated cataract surgery by phacoemulsification in non-glaucomatous PXS subjects.
The study population includes patients with PXS and concurrent cataract who were referred to the glaucoma clinic of Farabi Eye Hospital, Tehran, Iran, for cataract extraction from April 2013 to February 2015. The study protocol followed the tenets of the Declaration of Helsinki and was approved by the Research Ethics Committee. Written informed consent was obtained from all patients prior to enrolment.
Inclusion criteria were: (1) visible evidence of pseudoexfoliation material on either the anterior lens capsule or pupillary margin on dilated slit-lamp examination; (2) absence of glaucomatous appearance of the optic disc (defined as an intact neuroretinal rim without cupping, notches or localised pallor); (3) normal results of standard automated perimetry and (4) visually significant cataract with best-corrected visual acuity worse than 20/30.
Exclusion criteria included: (1) ocular history of any laser procedure or incisional surgery; (2) history of acute IOP elevation; (3) IOP >30 mm Hg and (4) inability to complete study procedures.
Preoperative and postoperative evaluation
Prior to cataract surgery, all subjects underwent a routine ophthalmic examination, which included visual acuity testing, slit lamp examination, IOP measurement by Goldmann applanation tonometry, dilated funduscopy, central corneal thickness measurement by ultrasound pachymetry (Sonomed 200P+ Micropach, Sonomed, New Hyde Park, NY, USA) and axial length measurement (Echoscan, model U3300, Nidek, Tokyo, Japan). A glaucoma specialist (SM) performed gonioscopy using a Zeiss-style 4-mirror goniolens (Model G-4; Volk Optical, Mentor, OH, USA) with a narrow 1 mm beam of light. A vertical beam was used to evaluate the superior and inferior angles, whereas a horizontal beam was used for the nasal and temporal angles. Gonioscopic grading of the angle was done according to the Schaffer grading system. After mydriasis, crystalline lens nucleus density was graded according to the Lens Opacities Classification System III.22
Visual field was evaluated with the Humphrey VF analyzer (central 24-2 SITA standard programme; Carl Zeiss Meditec, Dublin, CA, USA). Criteria to establish the reliability of visual field data were rates of fixation loss, false negatives <25% and false positives <15%.
To maximise the accuracy of IOP measurements, the same ophthalmologist (SM) measured IOP twice for each eye between 9:00 and 12:00 during preoperative and postoperative visits. From the two IOP measurements, a mean IOP value was derived for statistical analysis. If the two IOP values differed by more than 2 mm Hg, the ophthalmologist would perform a third IOP measurement, and the median value was used in analysis.
All subjects underwent standard clear corneal incision phacoemulsification. The same phacoemulsification machine used was used in all cases (Model Infiniti; Alcon Laboratories, Fort Worth, TX, USA). One surgeon (SM) performed all operations under topical anaesthesia. The surgeon first created a paracentesis and injected viscoelastic into the anterior chamber. A temporal 3 mm wide by 2 mm long clear corneal incision was performed. Iris retractors were inserted without mydriasis with intracameral epinephrine or atropine. A continuous curvilinear capsulorrhexis measuring approximately 5.0 mm in diameter was achieved with a cystotome. Hydrodissection and hydrodelineation were then performed, and the nucleus was removed using a chopping technique. The capsular bag was filled with viscoelastic after removal of the epinucleus and cortex using the phacoemulsification handpiece. A single-piece foldable acrylic posterior chamber intraocular lens (Model SA60AT; Alcon Laboratories) was implanted into the capsular bag, and finally viscoelastic was removed from the eye. Wounds were left unsutured.
The intraoperative metrics from the phacoemulsification machine were recorded at the end of each surgery. Routine postoperative examination and follow-up were performed at 1 day, 1 week, 1 month and 3 months postoperatively.
Anterior segment optical coherence tomography
ASOCT imaging was performed by experienced operators at 1 day before and 3 months after cataract surgery (Visante OCT; Carl Zeiss Meditec) in dark ambient lighting (a windowless room, with the door closed and the only lightening was the ASOCT screen). The image frame was centred on the pupil, and the Enhanced Anterior Segment Single Protocol was used to obtain the scans. Three images were captured using this protocol. The principal investigator (SM) validated all the images for quality and scleral spur location and selected the highest quality image for each eye to use for analysis using the Zhongshan Angle Assessment Program (ZAAP, Guangzhou, China). Images were excluded if they had poor quality, poor perpendicularity or inability to locate scleral spurs. ZAAP is a specialised software that automatically measures various anterior segment parameters after the operator identifies the location of the scleral spurs. The anatomic parameters include ACD, anterior chamber area (ACA), anterior chamber width (ACW), iris thickness (IT), iris area, iris curvature, lens vault (LV) and various angle parameters, including angle opening distance at 500 and 750 microns from the scleral spur (AOD500, AOD750) and trabecular iris space area at 500 and 750 microns from the scleral spur (TISA500, TISA750). Table 1 lists the definitions of the ASOCT parameters analysed in this study.23–26
The main outcome variable was IOP change at 3 months postoperatively. Eyes that required a mechanical device for pupil dilation intraoperatively and eyes with unqualified ASOCT images were excluded from the final analysis. Descriptive statistics were performed to characterise the study sample. The mean and SDs were calculated for the continuous variables. All statistical analyses were performed using non-parametric tests. The Wilcoxon signed rank test was use to compare mean values before and after cataract surgery.
Univariate regression was performed between potential cofounders and IOP change. Multivariate linear regression models that adjusted for sex, age and preoperative IOP were used to evaluate predictors of IOP change after phacoemulsification. To take into consideration the effect of pupil diameter on angle and iris parameters, comparison for these measurements was performed with adjustment for pupil diameter using analysis of covariance test. A final multivariate regression model was built by first adjusting for age and sex and then adding any other potential confounders with both p<0.20 in univariate analysis and variance inflation factor <3. The regression coefficients (B), coefficients of determination (R2) and statistical significance (p value) were reported. p Values ≤0.05 were considered significant. All statistical analysis was performed using SPSS software V.18 (SPSS, Chicago, IL, USA).
A total of 43 patients with PXS were consecutively enrolled and underwent cataract surgery by phacoemulsification. Among them, 10 patients were excluded due to unqualified images (3 patients), loss to follow-up (4 patients) or requiring mechanical device for pupil dilation during surgery (3 eyes). The final sample included 33 eyes of 33 patients with a mean age of 75.4±6.5 years. The 33 patients comprised 20 men and 13 women.
Table 2 summarises the clinical characteristics and intraoperative phacoemulsification metrics of our study cases. Twenty-two eyes had open angles and 11 eyes had narrow angles upon gonioscopy. Before cataract surgery, the mean IOP was 18.1±3.4 mm Hg, which decreased by 3.3 mm Hg (18%) to 14.8±3.6 mm Hg at 3 months (p<0.001). The amount of IOP drop was not significantly different between narrow angles and open angles (−3.18±3.92 vs 3.50±5.2 mm Hg, p=0.85).
Table 3 presents the ASOCT findings before and after surgery. Phacoemulsification resulted in increases in all anterior chamber angle parameters, ACD and ACA (p<0.001 for all). We also found an increase in iris area postoperatively (p=0.03). Iris curvature decreased postoperatively (p<0.001), and there was no significant change in ACW and IT750.
Predictors of postoperative intraocular pressure
Table 4 shows the univariate predictors of the change in IOP at 3 months. Preoperative IOP (B=−0.668, p=0.002), infusion fluid usage (B=−0.040, p=0.04) and aspiration time (B=−0.045, p=0.003) were negatively correlated with IOP decrease after phacoemulsification (figure 1). Higher preoperative IOP, greater infusion fluid usage and greater aspiration time during surgery led to greater IOP drop. Changes in IOP did not demonstrate significant associations with CDE or ASOCT measurements, including preoperative AOD750, ACD, ACA, ACW, LV, IT, iris area, iris curvature and change in AOD750.
After adjusting for the effects of age, sex and preoperative IOP, infusion fluid usage and aspiration time predicted 34.9% (p=0.004), 19.6% (p=0.05) and 31.2% (p=0.004) of the variation in postoperative mean IOP, respectively.
After adjusting for sex, age and preoperative IOP, two variables were significantly associated with postoperative IOP change: infusion fluid usage and aspiration time. In the final regression model that included age, sex and any potential confounders with p<0.20 in univariate analysis and variance inflation factor <4, preoperative IOP (B (95% CI)=−0.668 (−1.059 to −0.276), p=0.002) and infusion fluid usage (B (95% CI)=−0.041 (−0.081 to −0.002), p=0.04) were significantly associated with IOP drop. Together, preoperative IOP and infusion fluid usage predict 45.1% of variability in IOP change (p=0.002).
In the present study, postoperative IOP decreased 18.1% from preoperative values at 3 months after cataract surgery in non-glaucomatous PXS subjects. This IOP response was negatively associated with preoperative IOP, aspiration time and infusion fluid usage. Higher preoperative IOP, greater infusion fluid usage and greater aspiration time during surgery led to greater IOP drop. Anterior chamber angle parameters and depth as well as ultrasound energy used during phacoemulsification did not predict postoperative IOP.
The amount of IOP reduction after cataract surgery (18.1%) in our study population is within the range of postoperative IOP change previously reported in patients with PXS. In a report by the American Academy of Ophthalmology that evaluated papers with higher levels of evidence, the average amount of IOP drop after phacoemulsification in PXS was shown to be approximately 20%. Georgopoulos et al27 prospectively studied controlled pseudoexfoliative glaucoma cases and demonstrated that cataract surgery resulted in an IOP drop from 18.7 to 16.7 mm Hg, a reduction of 2.0 mm Hg (11%). In another study by Damji et al6 on Greek, Canadian and American patients with mild pseudoexfoliative glaucoma, phacoemulsification resulted in long-term postoperative IOP reduction of 16% from 19.8 to 16.7 mm Hg.
Although the mechanisms of IOP reduction after phacoemulsification are not fully understood, two current theories suggest that postoperative improvements in TM function and aqueous humour access to the TM may be responsible.28 However, the dominant mechanism may vary across different types of glaucoma. The amount of IOP drop following phacoemulsification has been shown to be greater in patients with exfoliation syndrome (XFS) compared with eyes without XFS.5 ,6 In a study by Damji et al,6 IOP response in patients with XFS correlated with the volume of irrigation fluid used intraoperatively. They speculated that the procedure may remove pigment and exfoliation material from the outflow system, thus leading to greater IOP reduction in patients with XFS. This hypothesis has been supported by previous studies,27 ,29 which advocated the use of anterior chamber irrigation with a trabecular aspiration device in pseudoexfoliation glaucoma after demonstrating that it results in significant IOP reduction over a 2-year follow-up period. Consistent with these studies, the IOP drop in our patients was independently associated with aspiration time and infusion fluid usage.
The results of our univariate and multivariate linear analyses demonstrated no relationship between the amount of ultrasound energy delivered to the eye during phacoemulsification, expressed as CDE, and postoperative IOP reduction. Wang et al30 previously showed that interleukin (IL)-1α could be induced in TM cells by ultrasound energy during phacoemulsification. This mediator has been shown to promote IOP reduction by inducing synthesis of matrix metalloproteinases, which in turn enhance the degradation of extracellular matrix and increase outflow facility. However, currently no clinical study has addressed IL-1α release from exposure to ultrasound energy as one of the mechanisms behind IOP reduction. Consistent with our findings, a recent study on non-PXS subjects did not find any association between CDE and postoperative IOP change.28
Preoperative IOP is the only consistent established predictor of IOP change after phacoemulsification in both non-glaucomatous and glaucomatous eyes in the literature. IOP drop is greater in eyes with higher preoperative IOP values in PACG, POAG and OHT eyes. When the IOP is close to episcleral venous pressure, IOP cannot decrease further as there is little resistance to aqueous outflow. In different studies, preoperative IOP value can predict 20%17 to 40%8 ,9 of the variation in postoperative IOP. In a study by Shingleton et al8 on 882 eyes with PXS, higher preoperative IOP was associated with a greater reduction in IOP. In our studies, preoperative IOP was the main predictor of IOP change after phacoemulsification and was associated with 39% of the variation in IOP change.
The crystalline lens has a pivotal role in angle narrowing by pushing the peripheral iris anteriorly.11 ,31 Cataract extraction is one of the few modifiable factors that can deepen the anterior chamber and open the iridocorneal angle, thus changing12 ,16 ,20 ,32 IOP. This effect is more exaggerated in angle closure eyes.5 ,12 ,13 ,15 ,33–35 These eyes tend to have thicker lens, which occupy a more anterior position in these eyes compared with normal eyes.23 ,36 ,37 Some have considered changes in anterior chamber angle and depth to be the main mechanism of IOP lowering after phacoemulsification in these eyes.12 ,18 ,35 Huang et al11 ,12 showed that IOP lowering is related to the angle opening induced by cataract surgery; postoperative IOP drop was greater in eyes with narrow angles than eyes with open angles because of the greater angle increase. For PACG, some studies have shown that IOP reduction is associated with ACD, and a narrower preoperative angle and a greater change in ACD are associated with greater IOP drop after cataract surgery.19 ,38
There is no study in published literature investigating the effects of phacoemulsification on the drainage angle in PXS eyes. In the present study, we report increases in angle width and in ACD and area after cataract surgery. We did not find any association between angle, lens and anterior segment parameters with postoperative IOP change. The lack of an association between postoperative IOP and preoperative anterior segment angle width and ACD, both in this study and in previous studies on open angle eyes, suggests that mechanisms of IOP reduction other than macroscopic angle closure may be at play.17 ,33 ,34 ,39 This is especially true in PXS eyes in which microscopic TM changes and clogging may be implicated in the development of IOP rise. These microscopic TM changes may be partially resolved by irrigation during phacoemulsification. In fact, our study shows that preoperative IOP and infusion fluid usage together can predict approximately 45% of the variation of the IOP drop.
Our study showed the iris profile becomes flatter after cataract surgery in PXS eyes. Although we could not measure iris-lens contact with ASOCT, it might be relevant to note that cataract surgery eliminates iridolenticular friction and thus significantly reduces the release of pigment from the iris and exfoliation material from the lens and iris. The decreased iridolenticular contact may contribute to the longer-term IOP drop seen in patients with XFS.
Previous reports on Iranian population showed a 13%–25% IOP reduction after cataract surgery in open angles, which is comparable to our patients with PXS.20 ,40 However, most of the studies on other ethnicities that compared the effect of phacoemulsification in PXS eyes and open angles showed that IOP reduction is greater in the PXS eyes.5 Differences in baseline characteristics of patients and difference in the designs and setting of the studies on Iranian eyes may be a reason for this discrepancy. Similar to investigations in other population, the amount of IOP reduction in PXS eye (18%) were less than what were reported in Iranian population narrow angles (30%–35%).13 ,20
Endothelial cell damage should be taken into account in any intraocular surgeries. Several clinical studies have found decreased corneal endothelial cell density in eyes with PXS.41 ,42 Although some reports showed that endothelial cell loss after cataract surgery in eyes with PXS does not differ significantly from that in eyes without PXS,43 other investigators found a decrease in endothelial cell count in patients with PXS regardless of the phaco time, irrigation volume and surgical intervention.41 ,44 Hayashi et al44 demonstrated that corneal endothelial damage did not differ markedly between eyes with glaucoma and those without glaucoma. However, they did not evaluate association of irrigation volume during phacoemulsification and amount of endothelial damage.
This study has some limitations that should be kept in mind. We did not have data on lens thickness and were unable to measure lens-iris contact with ASOCT. In addition, a longer follow-up would allow evaluation of the long-term associations of intraoperative metrics, preoperative anterior segment dimensions and postoperative IOP change. Finally, with a relative small size and absence of normal control subjects, it might be difficult to generalise our findings to the entire Iranian population or other ethnicities.
In summary, the present study demonstrates that non-glaucomatous patients with PXS have a moderate IOP-lowering effect following phacoemulsification and that this effect is correlated with preoperative IOP and intraoperative aspiration time and infusion fluid usage.
We thank Nassim Khatibi for assistance in data collection and tabulation.
Contributors Involved in conception and design of study (SM and SCL); data collection (SM, MJ, AM and MM); analysis and interpretation of data (MJ, SM, AM, RC and SCL); provision of materials, patients or resources (SM and MH); statistical expertise (SM, RC and MJ); literature search (RC and SM); administrative, technical or logistic support (SM); writing the article (SM); critical revision of article (RC) and final approval of it (all authors). The protocol of the study was approved by the institutional review board of Farabi Eye Hospital, Tehran, Iran. Written informed consent was obtained from all the participants after complete explanation.
Competing interests None declared.
Patient consent Obtained.
Ethics approval Farabi Eye Hospital.
Provenance and peer review Not commissioned; externally peer reviewed.
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