Primary angle-closure glaucoma (PACG) occurs when

Transcription

1 ORIGINAL STUDY Phacoemulsification Versus Combined Phacoemulsification and Viscogonioplasty in Primary Angle-Closure Glaucoma: A Randomized Clinical Trial Sasan Moghimi, MD,*w Golshan Latifi, MD,* Narges ZandVakil, MD,* Massood Mohammadi, MD,* Nassim Khatibi, BA,* Reza Soltani-Moghadam, MD,* and Shan Lin, MDw Purpose: To compare the effect of phacoemulsification (Phaco) versus combined phacoemulsification and viscogonioplasty (Phaco- VGP) on long-term intraocular pressure (IOP) in primary angleclosure glaucoma (PACG). Methods: In this prospective randomized clinical trial, 92 eyes of 82 patients with PACG and coexisting cataract were randomized to undergo Phaco alone (46 eyes) or Phaco-VGP (45 eyes) and completed the trial. Anterior segment optical coherence tomography was performed preoperatively and at 1 year after surgery. Main outcome measures were IOP and the number of IOP-lowering medications. Results: Phaco alone reduced the mean IOP from a preoperative level of 22.3 ± 6.3 to 14.0 ± 3.7 mm Hg at 12 months after surgery (P < 0.001). Phaco-VGP reduced the mean IOP from a preoperative level of 23.3 ± 7.3 to 14.5 ± 2.5 mm Hg (P < 0.001). There were no statistically significant differences between the 2 groups in IOP and number of medications at all follow-up times. Trabecular-iris space-area measured by anterior segment optical coherence tomography increased significantly after Phaco alone and Phaco-VGP. The amount of the increase was higher in the Phaco-VGP. Although peripheral anterior synechiae (PAS) extent decreased significantly by Phaco alone, Phaco-VGP resulted in significantly greater reduction in PAS extent (P = 0.004). The only variables that predicted change in IOP in the whole group were preoperative IOP (b = 0.891, P < 0.001) and female sex (b = 2.754, P = 0.02). Conclusions: Phaco alone and Phaco-VGP resulted in widening of the drainage angle, reduction of IOP, and PAS extent in PACG eyes. Phaco-VGP resulted in significantly more reduction of PAS and more opening of angle. However, it seems that additional VGP has no significant effect on long-term IOP. Key Words: phacoemulsification, viscogonioplasty, primary angleclosure glaucoma, anterior segment optical coherence tomography, anterior chamber depth, intraocular pressure (J Glaucoma 2014;00: ) Received for publication February 15, 2014; accepted October 8, From the *Farabi Eye Research Center, Tehran University of Medical Science, Tehran, Iran; and wdepartment of Ophthalmology, San Francisco School of Medicine, University of California, San Francisco, CA. Disclosure: The authors declare no conflict of interest. Reprints: Sasan Moghimi, MD, Farabi Eye Research Center, Tehran University of Medical Sciences, Qazvin Sq., South Kargar Ave. Tehran , Iran ( sasanimii@yahoo.com). Copyright r 2014 by Lippincott Williams & Wilkins DOI: /IJG Primary angle-closure glaucoma (PACG) occurs when the anterior chamber (AC) drainage angle progressively narrows with a subsequent rise in intraocular pressure (IOP) leading to glaucomatous optic neuropathy. 1 Recent evidence indicates that a thickened and anterior-positioned lens plays a crucial role in the pathogenesis of PACG, especially in elderly individuals, and that lens extraction is effective in deepening the AC, opening the iridocorneal angle, and lowering the IOP. 2 7 However, in chronic cases the trabecular meshwork may remain occluded by peripheral anterior synechiae (PAS) despite AC deepening. In these eyes the trabecular meshwork can be exposed again if PAS are broken by separating the adherent iris from the meshwork. Theoretically, goniosynechialysis can restore trabecular function in eyes with PACG by stripping PAS from the angle and exposing the underlying trabecular meshwork Although viscogonioplasty (VGP) has been introduced for breaking PAS in PACG by using heavy viscoelastics like Healon [Abbott Medical Optics (AMO), Abbott Park, IL], 9 13 recurrence of PAS or permanent damage to the trabecular meshwork might cause the goniosynechialysis to fail to regain aqueous outflow in the long term. 14,15 In the literature combined phacoemulsification (Phaco) and viscogoniosynechialysis was an effective and safe treatment for management of angle-closure glaucoma. 9 13,16 Our previous publication revealed that goniosynechialysis may have some additional effect on drainage angle anatomy. 17 However, few studies have assessed the effect of additional goniosynechialysis to Phaco on long-term IOP in PACG patients. The objective of this randomized clinical trial is to compare the effects of Phaco alone versus combined phacoemulsification and viscogonioplasty (Phaco-VGP) on long-term IOP and anterior segment parameters in PACG eyes. We used anterior segment optical coherence tomography (AS-OCT) to assess the AC and angle parameters, and evaluated the variables that affect IOP control in PACG eyes after Phaco. This device provides a noncontact assessment of the AC and angle parameters, and allows users to quantify angle width and measure AC dimensions and parameters including novel factors such as lens vault (LV), thus helping researchers in further understanding the pathogenesis of anterior segment disease PATIENTS AND METHODS This was a prospective randomized clinical trial conducted in Farabi Eye Hospital, Tehran, Iran. The Farabi Angle Closure Study (FACS) protocol followed the tenets J Glaucoma Volume 00, Number 00,

2 Moghimi et al J Glaucoma Volume 00, Number 00, 2014 of the Declaration of Helsinki and was approved by the Farabi Hospital Research Ethics Committee and registered with Iranian Registry of Clinical Trial (IRCT). Patients visiting the glaucoma clinic, from October 2009 to February 2012 were prospectively enrolled in the study if they met the inclusion and exclusion criteria. Written informed consent was obtained from all patients before enrollment. Inclusion criteria included: (1) PACG defined by at least 270 degrees of iridotrabecular contact (appositional or synechial on gonioscopy) and glaucomatous optic neuropathy determined by optic disc cupping and glaucomatous visual field loss; (2) synechial closure of at least 90 degrees; (3) visually significant cataract with best-corrected visual acuity (VA) of worse than 20/30; (4) IOP < 35 mm Hg; and (5) patent peripheral iridotomy. Exclusion criteria were: (1) eyes with a history of an acute or subacute attack of angleclosure glaucoma; (2) presence of any cause of secondary glaucoma including uveitic glaucoma, neovascular glaucoma, exfoliative glaucoma, and phacomorphic glaucoma; and (3) history of any previous incisional eye surgery. Examinations included VA testing with manifest refraction, IOP measurement by Goldmann applanation tonometry, complete slit-lamp and fundus examination, and gonioscopy (described in detail below). IOP measurement, optic disc evaluation, and gonioscopy were performed by a single glaucoma specialist (G.L.). Additional preoperative data gathered included demographic information and antiglaucoma medications. For all patients, axial length and lens thickness were measured using A scan ultrasound (Echoscan, model U3300; Nidek Inc., Tokyo, Japan). Gonioscopy Subjects underwent gonioscopy preoperatively and during follow-up visit, by a single glaucoma specialist who was masked to the AS-OCT images and findings. Patients were examined in low light conditions with a Zeiss-style 4- mirror goniolens (Model G-4; Volk Optical, Mentor, OH). A narrow 1-mm beam of light was USED; a vertical beam was used to evaluate the superior and inferior angles, whereas a horizontal beam was used for the nasal and temporal angles. All 4 quadrants were assessed with the eye in the primary position of gaze; slight tilting of the lens was allowed if there was significant LV. The angle was graded using the Spaeth grading system. Average of the gonioscopic grading in the 4 quadrants was defined as the gonioscopic grade for each eye. 19 Indentation gonioscopy was used to establish the presence and extent of PAS. PAS were defined as abnormal adhesions of the iris to the angle to the level of the trabecular meshwork, which are at least 15 degrees in width and could not be broken with indentation gonioscopy. The extent of PAS was noted in degrees. The data from last visit was used for statistical analysis. 21 AS-OCT AS-OCT (Visante OCT; Carl Zeiss Meditec, Dublin, CA) was performed for all the patients preoperatively and 1 year after surgery, under dark conditions. Scans were centered on the undilated pupil, and were obtained along horizontal and vertical axes using the enhanced anterior segment single protocol. The same examiner, who was masked to clinical findings, obtained all images. Three consecutive images were captured, and the image with the best quality regarding centration and visibility of the scleral spurs was chosen for analysis. Measurements were conducted by 2 observers who were masked to the patients gonioscopy findings and type of intervention. Although images of all 4 angle quadrants were captured, images of the inferior and superior quadrants were not included in the analysis because of suboptimal image quality and previously reported poor reproducibility of the measurements. Angle parameters measured were trabecular-iris space area (TISA) at 500 and 750 mm from the scleral spur, in the temporal and nasal quadrants. The mean of the nasal and temporal TISA500 and TISA750 were labeled as TISA500 and TISA750, respectively. AC depth was defined as the distance from the endothelium at the center of the cornea to the anterior pole of the cataractous lens or intraocular lens (IOL). LV was defined as the perpendicular distance between the anterior lens surface to the horizontal line connecting the 2 scleral spurs, 20 and was measured by the chamber tool of the machine. Randomization of Subjects and Sample Size Patients were randomized into 2 groups using computer-generated random blocks to receive either cataract extraction alone (Phaco alone group) or cataract extraction with VGP (Phaco-VGP group). An investigator with no clinical involvement in the trial consecutively assigned each patient enrolled by the clinical investigators to one of the 2 groups according to the random blocks. Patients and clinical investigators who performed gonioscopy, AS-OCT, and IOP measurement were masked to the treatment arm. Cataract Surgical Technique Surgery was performed by a single surgeon (S.M.) in all subjects under topical anesthesia. Surgery consisted of routine Phaco (phaco chop technique) through a 3.2-mm temporal clear corneal incision, with an in-the-bag onepiece acrylic IOL (AcrySof SA60AT; Alcon Laboratories Inc., Fort Worth, TX) implantation. Cohesive viscoelastic (Amvisc; Bausch & Lomb Inc., Rochester, NY) was used before capsulorhexis to deepen but not overfill the AC. Fritz Ruck Pentasys 2 (Ophthalmologische Systeme GmbH, Eschweiler, Germany) was used in all cases, with a vacuum of 350 mm Hg, maximum ultrasound power of 30%, and an IOP-set of 70 mm Hg. VGP Technique Following IOL implantation a cohesive viscoelastic (Amvisc; Bausch & Lomb Inc.) was used to deepen the AC and was then injected near the angle for 360 degrees twice without touching the angle with the cannula. Synechalysis in the inferior, nasal, and superior angles was performed through the temporal corneal incision. Synechalysis in the temporal quadrant was performed through the side port. No surgical instruments were used to physically break the PAS. After completion of VGP, the viscoelastic was meticulously removed. All patients received oral acetazolamide 250 mg 3 times a day for 24 hours, topical antibiotics 4 times a day for 1 week, as well as topical 1% prednisolone acetate every 2 hours which was tapered gradually over 1 month. Antiglaucoma medications were discontinued postoperatively and restarted if needed. Randomization of Subjects and Sample Size The primary outcome measures were IOP and the number of IOP-lowering medications after 1 year. For an SD of 3 mm Hg, we needed 37 patients in each group to 2 r 2014 Lippincott Williams & Wilkins

3 J Glaucoma Volume 00, Number 00, 2014 Phaco Versus Phaco-VGP in PACG achieve an 80% power to detect a difference of 2 mm Hg in final IOP between the 2 groups with a P-value of Secondary outcome measures included angle and anterior segment parameters, amount of synechial closure, and surgical complications. One investigator, who was masked to the surgery performed, examined all patients postoperatively on the first day, and at week 1; months 1, 3, and 6; and 1 year. IOP, number of IOP-lowering drugs needed, best-corrected VA, and complications were recorded. IOP at 1 year was considered as the final IOP for analysis. Statistical Analysis Statistical analysis was performed using SPSS software, version 17 (SPSS Inc., Chicago, IL). Student t and w 2 tests were used for comparing parametric quantitative and qualitative variables between groups, respectively. The paired t test was used to compare differences between preoperative and postoperative parametric data in the same group. For nonparametric variables, Mann-Whitney U test used. The Pearson correlation was used to assess the associations between preoperative variables and the changes in IOP. Linear regressions were performed with change in IOP as the dependent variables and the relevant predictive factors as covariates. Finally age, sex, and factors significant at a level of P < 0.20 in linear regression were included in the multivariate regression analysis. P-value of <0.05 was considered statistically significant. The data from the patients who had major intraoperative or postoperative complications (eg, vitreous loss or endophthalmitis) were not included for the analysis. RESULTS Of 101 eyes, 91 eyes of 82 patients with PACG and coexisting cataract completed this randomized clinical trial study (Fig. 1). Of these 91 eyes, 46 were randomized into the Phaco alone treatment group and 45 were randomized into the Phaco-VGP treatment group. The demographic characteristics and baseline clinical status are shown in Table 1. There was no statistically significant difference between the groups according to these baseline characteristics. VA increased significantly in the Phaco alone and Phaco-VGP groups. Figure 2 compares the IOP profiles of the 2 groups of patients. Phaco alone reduced the mean IOP from a preoperative level of 22.3 ± 6.3 mm Hg (range, 10.0 to 34.0 mm Hg) to 14.0 ± 3.7 mm Hg (range, 9.0 to 24.0 mm Hg) at 12 months after surgery, that is, a 37% reduction (P = 0.001, paired t test). Phaco with adjunctive VGP reduced the mean IOP from a preoperative level of 23.3 ± 7.3 mm Hg (range, 10.0 to 34.0 mm Hg) to 14.5 ± 2.5 mm Hg (range, 10 to 21 mm Hg) at 12 months after surgery, that is, a 38% reduction (P = 0.001, paired t test). In both the groups the mean postoperative IOPs at all postoperative time points up to 12 months were statistically significantly lower (P < 0.001, paired t test) than the mean preoperative IOP. However, there were no statistically significant differences between the 2 groups in IOP at all follow-up times (Table 2). This is also true for change in IOP at final follow-up compared to preoperative values ( 8.3 ± 6.8 vs. 8.8 ± 8.4 mm Hg for Phaco and Phaco- VGP groups, respectively). Both groups had significantly reduced mean number of glaucoma medications at all postoperative times compared with their preoperative status (P < 0.001) (Table 2). However, there were no statistically significant differences between the 2 groups in terms of number of medications at all follow-up times. Table 3 summarizes the preoperative and postoperative gonioscopic and AS-OCT findings in the 2 treatment groups. There was no statistically significant difference between the 2 groups in the extent of synechial angle closure before surgery or 1 year after surgery (P = 0.30 and P = 0.28, respectively). However, within both the treatment groups, there was a statistically significant reduction in the mean extent of synechial angle closure at final follow-up, compared with the preoperative extent (P < for both groups). Moreover, the amount of change in PAS in the Phaco-VGP group was significantly greater than in the control group (P = 0.004). Gonioscopic measurements indicated an improvement in angle width in both the groups (P < for both). TISA500 and TISA750 measured by AS-OCT increased significantly in both groups after surgery. However, the amount of the increase was significantly higher in the Phaco-VGP (P = 0.04 and P = 0.03, for TISA500 and TISA750, respectively). In whole group, the amount of decrease in IOP at 1 year correlated only with preoperative IOP (correlation coefficient = 0.91, P < 0.001) (Fig. 3). After multivariable regression, preoperative IOP (b = 0.891, P < 0.001) and female sex (b = 2.75, P = 0.02) were the only variables that were associated with changes in IOP after 1 year (Table 4). None of the cases developed vitreous loss or endophthalmitis. Four patients in the Phaco-VGP and 2 in the Phaco alone group developed fibrin reaction postoperatively that resolved after a few days. There were no prolonged uveitic episodes or significant iris trauma documented postoperatively. In addition, 3 patients in the Phaco-VGP group developed hyphema intraoperatively that subsided within seconds by viscotamponade. DISCUSSION In this randomized controlled study of the effect of adjunctive VGP on IOP, we found a 37% and 38% decrease in IOP in the Phaco alone and Phaco-VGP groups, respectively. Although the change in IOP was not significantly different between groups, the Phaco-VGP group showed significantly greater changes in angle parameters and amount of synechial closure reduction. The occurrence of PACG is often associated with the specific anatomic structures of the anterior segment of the eye, including a shallow AC, a narrow angle, and a thick and anteriorly positioned lens. 2,4,7,20,21 In the past, the preferred practice was to perform cataract extraction combined with trabeculectomy in PACG patients who have a visually significant cataract in association with uncontrolled IOP. 22,23 However, this combined procedure carries a significant risk of developing postoperative complications like flat AC, bleb leak, malignant glaucoma, and choroidal effusion. 24,25 On the basis of 2 recent related randomized clinical trials, it appears that phacoemulsification alone is a reasonable surgical alternative to combined phacotrabeculectomy in PACG eyes, whether the preoperative IOP is medically controlled or not. 25,26 Consistent with our study, Tham and colleagues showed a 33% decrease in IOP after phacoemulsification r 2014 Lippincott Williams & Wilkins 3

4 Moghimi et al J Glaucoma Volume 00, Number 00, 2014 FIGURE 1. After excluding the patients who were with lost to follow-up, 50 eyes remained in the phacoemulsification (Phaco) group and 51 eyes remained in the Phaco and Viscogonioplasty (Phaco-VGP) group for final analysis. alone in their PACG patients. Although most of their cases had extensive PAS, they showed a statistically significant reduction in the mean extent of synechial angle closure at 1 year after surgery compared with the preoperative status from to 200 degrees The exact mechanism underlying this IOP reduction is not well understood. Phacoemulsification eliminates the pupillary block component and lessens angle crowding caused by a thick and anteriorly placed lens. 22 The deepening of the AC, the widening of the drainage angle, and the improved access of aqueous to the trabecular meshwork may all contribute to this IOP reduction. 3,28 31 However, in patients with PACG and PAS, the trabecular meshwork may remain occluded by PAS despite the AC deepening after Phaco alone. Potentially, the trabecular meshwork can be exposed by breaking PAS with goniosynechialysis. 8,23 Breaking PAS with goniosynechialysis and possible restoration of trabecular function before further irreversible structural changes progress seems to be a logical approach to the treatment of PACG. 1,15 Some investigators have evaluated the efficacy of VGP combined with cataract extraction in eyes with acute angle closure glaucoma (AACG) They reported a significant reduction in IOP from 52.1 to 14.1 mm Hg with no residual synechiae across 360 degrees of the angle. A few studies reported the effectiveness of this procedure in management of patients with PACG, as well. Razeghinejad and colleagues showed a significant reduction of IOP from 16.7 to 14.4 mm Hg and from to 15.5 mm Hg in medically controlled and uncontrolled patients, respectively. A significant number of their patients did not have PAS and they did not report the change in PAS or amount of open angle postoperatively. 32 In other studies on narrow-angle glaucoma patients, Phaco combined with goniosynechialysis appeared to not only lower IOP in the immediate postoperative period but also maintain a sustained effect over a significant period of time. 16 The same result was shown by Varma et al 9 who used viscoelastic for synechialysis during Phaco. We demonstrated a similar change in IOP between the Phaco alone and Phaco-VGP and this might suggest that IOP is not significantly improved by adding VGP when doing Phaco. Varma and colleagues showed in a randomized controlled trial of 50 eyes that there was a greater reduction in IOP in patients who had undergone Phaco and VGP than patients who had Phaco alone. However, the amount of PAS before and after surgery and the results of gonioscopic were not available. Including patients with AACG and excluding those with plateau iris syndrome 4 r 2014 Lippincott Williams & Wilkins

5 J Glaucoma Volume 00, Number 00, 2014 Phaco Versus Phaco-VGP in PACG TABLE 1. Demographics, Clinical Status, and Lens and Anterior Chamber Parameters in the Phaco Alone Group and Phaco- Viscogonioplaty Group Phaco Alone Phaco-VGP P No. eyes Mean age ± SD (range) (y) 63.2 ± 6.9 (50-79) 61.6 ± 8.3 (48-79) 0.44 Male to female ratio 19/27 19/ Follow-up (mo) Mean preoperative BCVA ± SD (range) (logmar) 0.49 ± 0.28 ( ) 0.49 ± 0.35 ( ) 0.98 Mean postoperative BCVA ± SD (range) (logmar) 0.27 ± 0.20 ( ) 0.28 ± 0.23 ( ) 0.85 Mean preoperative ACD ± SD (range) (mm) 2.36 ± 0.16 ( ) 2.35 ± 0.21 ( ) 0.85 Mean preoperative LT ± SD (range) (mm) 5.02 ± 0.31 ( ) 4.94 ± 0.48 ( ) 0.51 Mean preoperative LV ± SD (range) (mm) ± ( ) ± ( ) 0.44 ACD indicates anterior chamber depth; BCVA, best-corrected visual acuity; LT, lens thickness; LV, lens vault; Phaco, phacoemulsification; VGP, viscogonioplasty. might also be other reasons for their findings. 13 In fact, the procedure has been shown to be more effective in eyes with a previously documented acute symptomatic presentation of angle closure. 16 The results brought out the concept of trabecular function. When the trabecular meshwork function is subnormal, even if the drainage angle is open, the aqueous drainage outflow is still reduced. Theoretically, the longer duration the angle is closed, the higher the chance of trabecular dysfunction. Although some investigators reported a reduction of PAS extent after performing Phaco and goniosynechialysis in patients with AACG 8 or PACG, 17,32 mechanical deepening of the AC with viscoelastic and saline infusion during Phaco alone may also open some PAS. 33 In the present study, PAS extent decreased significantly after both procedures. However, the change in PAS extent in the Phaco-VGP group was significantly higher than in the Phaco alone group. Injection of high molecular weight viscoelastics near the angle seems to have additional effect in the reduction of PAS extent. It was not surprising to see that in both the procedures TISA500 and TISA750 increased and a significantly greater increase was observed in Phaco-VGP group. Interestingly, we found the preoperative angle findings was not a determinant of postoperative IOP in 1 year. Other studies also show little correlation between the degree of preoperative PAS and IOP control after cataract extraction in PACG. 34,35 Possible explanations include: (1) surgical manipulation, such as viscoelastic agent injection and positive flushing pressure may resolve those PAS that is of weak adherence 36 ; and (2) there is a similar amount of increase in angle parameters between those with PAS and without PAS. 30 Moreover, gonioscopic appearance may not truly reflect the extent of damage in the trabecular meshwork, the loss of trabecular cells, and the irregular architecture of the trabeculum that might exist in areas away from visible PAS or under the PAS. 37 The result of univariate analysis and multiple regressions showed a significant negative association between FIGURE 2. Intraocular pressure profiles of phacoemulsification (Phaco) alone (black line) and combined Phaco and Viscogonioplasty (Phaco-VGP (gray line) before and after surgery. There was no significant difference in intraocular pressure (IOP) before surgery and during follow-up between groups. The SD and number (N) of eyes at each follow-up period has been shown with the same color. r 2014 Lippincott Williams & Wilkins 5

6 Moghimi et al J Glaucoma Volume 00, Number 00, 2014 TABLE 2. Intraocular Pressure and Number of Glaucoma Drugs Before and After Surgery in the Phaco Alone Group and Phaco-VGP Group Phaco Alone Phaco-VGP P Mean preoperative IOP ± SD (range) (mm Hg) 22.3 ± 6.3 (10-34) 23.3 ± 7.3 (10-34) 0.59 Mean postoperative 1 mo IOP ± SD (range) (mm Hg) 15.5 ± 4.6 (9-24) 17.5 ± 4.7 (10-30) 0.11 Mean postoperative 3 mo IOP ± SD (range) (mm Hg) 14.6 ± 3.0 (8-20) 15.7 ± 3.5 (12-26) 0.30 Mean postoperative 6 mo IOP ± SD (range) (mm Hg) 13.9 ± 3.7 (10-24) 15.5 ± 3.3 (10-22) 0.18 Mean postoperative 1 y IOP ± SD (range) (mm Hg) 14.0 ± 3.7 (10-24) 14.5 ± 2.5 (10-21) 0.86 Final change IOP ± SD (range) (mm Hg) 8.3 ± 6.8 ( 20 to 4) 8.8 ± 8.4 ( 23 to 8) 0.87 P for final change in IO Mean preoperative no. glaucoma drugs ± SD (range) 1.2 ± 1.1 (0-3) 1.7 ± 1.1 (0-3) 0.09 Mean postoperative 1 mo no. glaucoma drugs ± SD (range) 0.0 ± 0.2 (0-1) 0.1 ± 0.4 (0-2) 0.06 Mean postoperative 3 mo no. glaucoma drugs ± SD (range) 0.1 ± 0.2 (0-1) 0.3 ± 0.7 (0-3) 0.26 Mean postoperative 6 mo no. glaucoma drugs ± SD (range) 0.1 ± 0.4 (0-1) 0.4 ± 0.8 (0-3) 0.37 Mean postoperative 12 mo no. glaucoma drugs ± SD (range) 0.1 ± 0.3 (0-1) 0.4 ± 0.8 (0-3) 0.14 P for final change in no. glaucoma drugs ± SD < < IOP indicates intraocular pressure; Phaco, phacoemulsification; VGP, viscogonioplasty. preoperative IOP and change in IOP. Many studies have shown that preoperative IOP is a good determinant of postoperative IOP in angle-closure disease with or without synechial closure. 35,37 Although some investigators demonstrated that greater lens thickness and LV are associated with greater IOP reduction postoperatively in POAG or narrow-angle eyes without synechiae, 3 in our results they were not associated with postoperative IOP change. Consistent with our results, Yudhasompop and Wangsupadilok 38 have shown no significant relationship between the decrease in IOP and lens thickness in 60 PACG patients with variable amount of PAS. In agreement with our study, AC depth was not a determinant of long-term IOP in their study as well. In our cases the drop in IOP was related to female sex. However, Huang and colleagues 3,28 did not show any association between sex and amount of IOP changes after cataract surgery. The reported complications with VGP include mild to severe hemorrhage from the iris or trabecular meshwork, fibrin exudation, iridodialysis, shallow AC, and transient elevation of IOP in the immediate postoperative period. Although Razeghinejad and Rahat 32 did not find any serious complications in their series of patients who underwent VGP, we encountered more fibrin reaction in the Phaco-VGP group compared to the Phaco alone group. However, VGP seems to be a much safer procedure than synechialysis done by knife or blunt spatula. The results of our study should be interpreted with its limitations in mind. One limitation of the AS-OCT used in this study is that it obtains a cross-section of the anterior segment along 1 meridian and is unable to adequately assess the extent of PAS. Although a glaucoma specialist measured PAS extent in degrees based on indentation gonioscopy, subjective evaluation of PAS might be an estimate and has some variability. Anterior segment sweptsource OCT, which was developed recently, has greater resolution and a much faster imaging speed based on Fourier-domain technology, making it possible to TABLE 3. Gonioscopic Angle Grading, Extent of Synechial Angle Closure, and AS-OCT Angle Parameters Before and After Surgery in the Phaco Alone Group and Phaco-VGP Group Mean ± SD Phaco Alone Phaco-VGP P Preoperative extent of PAS (deg.) ± (9-360) ± 91.3 (9-360) 0.30 Postoperative PAS (deg.) ± 95.6 (0-335) ± 88.3 (0-300) 0.28 Change in extent of PAS (deg.) 67.2 ± 84.1 ( 320 to 45) ± 56.9 ( 225 to 60) Preoperative angle grading 0.9 ± 0.7 (0-2.25) 0.6 ± 0.5 (0-1.75) 0.14 Postoperative angle grading 2.1 ± 1.0 (0-3.75) 2.5 ± 1.0 (0-4) 0.24 Change of angle grading 1.4 ± 0.8 (0-3.25) 2.0 ± 0.7 (0-3) 0.04 Preoperative TISA500 (mm) ± ± Postoperative TISA500 (mm) ± ± Change in TISA500 (mm) ± ± Preoperative TISA750 (mm) ± ± Postoperative TISA750 (mm) ± ± Change in TISA750 (mm) ± ± Average of the gonioscopic grading in Speath system in the 4 quadrants was defined as the gonioscopic grade for each eye. AS-OCT indicates anterior segment optical coherence tomography; Phaco, phacoemulsification; TISA, trabecular-iris space area; VGP, viscogonioplasty. 6 r 2014 Lippincott Williams & Wilkins

7 J Glaucoma Volume 00, Number 00, 2014 Phaco Versus Phaco-VGP in PACG FIGURE 3. Scatter plot showing negative correlation between change in intraocular pressure (IOP) 1 year after surgery and preoperative IOP in whole group (r = 0.91, P < 0.001). sequentially analyze a greater range of the angle and might be a better instrument for measuring change in iridotrabecular angle during follow-ups. For our study, we chose to perform only the standard horizontal scan as visibility of the vertical angles often requires manipulation of the eyelids which may affect the anterior segment and thus measurements of the angle parameters. Secondly, we evaluated the additional effect of viscosynechialysis to phacoemulsification; however, the results from this study may not be generalizable to the other methods of synechialysis such as manual ones. Finally, although we found only a difference of 0.5 mm Hg in IOP change between groups, our study had low power for detection of difference in the variable change in IOP (0.07). This might be due to high SD of IOP change in our cases in both the groups. In conclusion, our randomized clinical trial showed that both Phaco-VGP and Phaco alone resulted in reduction of IOP and glaucoma medications after 1 year, opening of the drainage angle, deepening of the AC, and reduction of PAS extent in PACG eyes. Although the changes in angle parameters were significantly higher when VGP was employed as an adjunct with phacoemulsification, IOP changes after 1 year were similar in both groups. TABLE 4. Linear Regression Analysis of the Association Between Preoperative Biometric Parameters and Final Change in Intraocular Pressure in Whole Group b SE P Age (y) Sex (female/male) Preoperative IOP (mm Hg) < Preoperative LV Group (VGP/Phaco) Preoperative extent of PAS (deg.) Preoperative TISA750 (mm) Preoperative ACD ACD indicates anterior chamber depth; IOP, intraocular pressure; LV, lens vault; PAS, peripheral anterior synechiae; Phaco, phacoemulsification; TISA, trabecular-iris space area; VGP, viscogonioplasty. REFERENCES 1. Lowe RF. Aetiology of the anatomical basis for primary angleclosure glaucoma. Biometrical comparisons between normal eyes and eyes with primary angle-closure glaucoma. Br J Ophthalmol. 1970;54: Friedman DS, Gazzard G, Foster P, et al. Ultrasonographic biomicroscopy, Scheimpflug photography, and novel provocative tests in contralateral eyes of Chinese patients initially seen with acute angle closure. Arch Ophthalmol. 2003;121: Huang G, Gonzalez E, Lee R, et al. Association of biometric factors with anterior chamber angle widening and intraocular pressure reduction after uneventful phacoemulsification for cataract. J Cataract Refract Surg. 2012;38: Moghimi S, Vahedian Z, Fakhraie G, et al. Ocular biometry in the subtypes of angle closure: an Anterior Segment Optical Coherence Tomography Study. Am J Ophthalmol. 2012;155: Shin HC, Subrayan V, Tajunisah I. Changes in anterior chamber depth and intraocular pressure after phacoemulsification in eyes with occludable angles. J Cataract Refract Surg. 2010;36: Tai MC, Chien KH, Lu DW, et al. Angle changes before and after cataract surgery assessed by Fourier-domain anterior segment optical coherence tomography. J Cataract Refract Surg. 2010;36: Wojciechowski R, Congdon N, Anninger W, et al. Age, gender, biometry, refractive error, and the anterior chamber angle among Alaskan Eskimos. Ophthalmology. 2003;110: Teekhasaenee C, Ritch R. Combined phacoemulsification and goniosynechialysis for uncontrolled chronic angle-closure glaucoma after acute angle-closure glaucoma. Ophthalmology. 1999;106: Varma D, Adams W, Phelan P, et al. Viscogonioplasty in patients with chronic narrow angle glaucoma. Br J Ophthalmol. 2006;90: Varma D, Baylis O, Wride N, et al. Viscogonioplasty: an effective procedure for lowering intraocular pressure in primary angle closure glaucoma. Eye. 2006;21: Fakhraie G, Vahedian Z, Moghimi S, et al. Phacoemulsification and goniosynechialysis for the management of refractory acute angle closure. Eur J Ophthalmol. 2012;155: Razeghinejad MR. Combined phacoemulsification and viscogoniosynechialysis in patients with refractory acute angleclosure glaucoma. J Cataract Refract Surg. 2008;34: r 2014 Lippincott Williams & Wilkins 7

8 Moghimi et al J Glaucoma Volume 00, Number 00, Varma D, Adams W, Bunce C, et al. Viscogonioplasty in narrow angle glaucoma: a randomized controlled trial. Clin Ophthalmol (Auckland, NZ). 2010;4: Gunning FP, Greve EL. Lens extraction for uncontrolled angle-closure glaucoma: long-term follow-up. J Cataract Refract Surg. 1998;24: Wishart P, Atkinson P. Extracapsular cataract extraction and posterior chamber lens implantation in patients with primary chronic angle-closure glaucoma: effect on intraocular pressure control. Eye. 1989;3: White AJ, Orros JMA, Healey PR. Outcomes of combined lens extraction and goniosynechialysis in angle closure. Clin Exp Ophthalmol. 2013;41: Eslami Y, Latifi G, Moghimi S, et al. Effect of adjunctive viscogonioplasty on drainage angle status in cataract surgery: a randomized clinical trial. Clin Exp Ophthalmol. 2013;41: Dada T, Sihota R, Gadia R, et al. Comparison of anterior segment optical coherence tomography and ultrasound biomicroscopy for assessment of the anterior segment. J Cataract Refract Surg. 2007;33: Lam DS, Leung DY, Tham CC, et al. Randomized trial of early phacoemulsification versus peripheral iridotomy to prevent intraocular pressure rise after acute primary angle closure. Ophthalmology. 2008;115: Nongpiur ME, He M, Amerasinghe N, et al. Lens vault, thickness, and position in Chinese subjects with angle closure. Ophthalmology. 2011;118: Su DH, Friedman DS, See JL, et al. Degree of angle closure and extent of peripheral anterior synechiae: an anterior segment OCT study. Br J Ophthalmol. 2008;92: Ho CL, Walton DS, Pasquale LR. Lens extraction for angleclosure glaucoma. Int Ophthalmol Clin. 2004;44: Lai JSM, Tham CCY, Lam DSC. The efficacy and safety of combined phacoemulsification, intraocular lens implantation, and limited goniosynechialysis, followed by diode laser peripheral iridoplasty, in the treatment of cataract and chronic angle-closure glaucoma. J Glaucoma. 2001;10: Moghimi S, Lin S. Role of phacoemulsification in angle closure glaucoma. Eye Sci. 2011;26: Tham CCY, Kwong YYY, Leung DYL, et al. Phacoemulsification versus combined phacotrabeculectomy in medically controlled chronic angle closure glaucoma with cataract. Ophthalmology. 2008;115: Tham CCY, Kwong YYY, Leung DYL, et al. Phacoemulsification versus combined phacotrabeculectomy in medically uncontrolled chronic angle closure glaucoma with cataracts. Ophthalmology. 2009;116: Tham CCY, Leung DYL, Kwong YYY, et al. Effects of phacoemulsification versus combined phaco-trabeculectomy on drainage angle status in primary angle closure glaucoma (PACG). J Glaucoma. 2010;19: Huang G, Gonzalez E, Peng PH, et al. Anterior chamber depth, iridocorneal angle width, and intraocular pressure changes after phacoemulsification: narrow vs open iridocorneal angles. Arch Ophthalmol. 2011;129: Issa S, Pacheco J, Mahmood U, et al. A novel index for predicting intraocular pressure reduction following cataract surgery. Br J Ophthalmol. 2005;89: Latifi G, Moghimi S, Eslami Y, et al. Effect of phacoemulsification on drainage angle status in angle closure eyes with or without extensive peripheral anterior synechiae. Eur J Ophthalmol [Epub ahead of print]. 31. Moghimi S, Latifi G, Amini H, et al. Cataract surgery in eyes with filtered primary angle closure glaucoma. J Ophthal Vis Res. 2013;8: Razeghinejad MR, Rahat F. Combined phacoemulsification and viscogoniosynechialysis in the management of patients with chronic angle closure glaucoma. Int Ophthalmol. 2010;30: Lai JSM, Tham CCY, Chan JCH. The clinical outcomes of cataract extraction by phacoemulsification in eyes with primary angle-closure glaucoma (PACG) and co-existing cataract: a prospective case series. J Glaucoma. 2006;15: Hayashi K, Hayashi H, Nakao F, et al. Effect of cataract surgery on intraocular pressure control in glaucoma patients. J Cataract Refract Surg. 2001;27: Liu CJ, Cheng CY, Wu CW, et al. Factors predicting intraocular pressure control after phacoemulsification in angle-closure glaucoma. Arch Ophthalmol. 2006;124: Spaeth GL. The clinical outcomes of cataract extraction by phacoemulsification in eyes with primary angle-closure glaucoma (PACG) and co-existing cataract: a prospective case series. J Glaucoma. 2006;15: Liu CJ, Cheng CY, Ko YC, et al. Determinants of long-term intraocular pressure after phacoemulsification in primary angle-closure glaucoma. J Glaucoma. 2011;20: Yudhasompop N, Wangsupadilok B. Effects of phacoemulsification and intraocular lens implantation on intraocular pressure in primary angle closure glaucoma (PACG) patients. J Med Assoc Thai. 2012;95: r 2014 Lippincott Williams & Wilkins