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Phacoemulsification versus Combined Phacotrabeculectomy in Medically Uncontrolled Chronic Angle Closure Glaucoma with Cataracts
Phacoemulsification versus Combined Phacotrabeculectomy in Medically Uncontrolled Chronic Angle Closure Glaucoma with Cataracts Clement C. Y. Tham, FRCS,1,2 Yolanda Y. Y. Kwong, MRCS,1,2 Dexter Y. L. Leung, FRCS,1,2 S. W. Lam, MRCS,1,2 Felix C. H. Li, MRCS,1,2 Thomas Y. H. Chiu, FRCS,1,3 Jonathan C. H. Chan, FRCS,1,4 Dennis S. C. Lam, FRCS, FRCOphth,1,2 Jimmy S. M. Lai, MD, FRCOphth4 Objective: To compare phacoemulsification alone versus combined phacotrabeculectomy in medically uncontrolled chronic angle closure glaucoma (CACG) with coexisting cataract. Design: Prospective randomized clinical trial. Participants: Fifty-one medically uncontrolled CACG eyes with coexisting cataract of 51 patients. Intervention: Recruited patients were randomized into group 1 (phacoemulsification alone) or group 2 (combined phacotrabeculectomy with adjunctive mitomycin C). Postoperatively, patients were reviewed every 3 months for 2 years. Main Outcome Measures: Intraocular pressure (IOP) and requirement for topical glaucoma drugs. Results: Twenty-seven CACG eyes were randomized into group 1, and 24 CACG eyes were randomized into group 2. Combined phacotrabeculectomy resulted in lower mean postoperative IOP than phacoemulsification alone at 3 months (14.0 vs. 17.0 mmHg, P ⫽ 0.01), 15 months (13.2 vs. 15.4 mmHg, P ⫽ 0.02), and 18 months (13.6 vs. 15.9 mmHg, P ⫽ 0.01). Combined phacotrabeculectomy resulted in 1.25 fewer topical glaucoma drugs (P⬍0.001) in the 24-month postoperative period, compared with phacoemulsification alone. Combined surgery was associated with more postoperative complications (P⬍0.001) and more progression of optic neuropathy (P ⫽ 0.03), compared with phacoemulsification alone. Conclusions: Combined phacotrabeculectomy with adjunctive mitomycin C is more effective than phacoemulsification alone in controlling IOP in medically uncontrolled CACG eyes with coexisting cataract. Combined phacotrabeculectomy is associated with more postoperative complications. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2009;116:725–731 © 2009 by the American Academy of Ophthalmology.
The prevalence of chronic angle closure glaucoma (CACG) increases with age, and CACG therefore frequently coexists with cataract. In such patients, it is common practice to perform combined cataract extraction and trabeculectomy (phacotrabeculectomy) to treat both diseases in one setting.1 Trabeculectomy, alone or in combination with other surgical procedures, is associated with a significant risk of complications. These include hypotony, shallowing of anterior chamber, malignant glaucoma, and endophthalmitis.2,3 A thick and anteriorly positioned lens has an important role in causing angle closure.4 –10 Lens extraction significantly widens the drainage angle11–14 and decreases intraocular pressure (IOP) in CACG eyes.11,15–23 Cataract extraction alone may therefore suffice as the primary treatment for CACG eyes with coexisting cataract, because it may treat both diseases at the same time. An earlier randomized controlled study compared the efficacy in IOP control of cataract extraction alone by © 2009 by the American Academy of Ophthalmology Published by Elsevier Inc.
phacoemulsification (phaco) versus combined phacotrabeculectomy with adjunctive mitomycin C chemotherapy in medically controlled CACG eyes with coexisting cataract.24 This article presents the results from a sister study that used the same study protocol but focused on another subgroup of patients with medically uncontrolled CACG eyes and cataract. “Medically uncontrolled” was defined as IOP greater than 21 mmHg despite maximally tolerated medications or requiring more than 3 topical drugs for IOP control.
Materials and Methods The authors obtained prior approval of the study protocol by the Ethics Committees of the Chinese University of Hong Kong, Hong Kong Eye Hospital, United Christian Hospital, and Prince of Wales Hospital. The research protocol adheres to the tenets of the Declaration of Helsinki. The study protocol was registered with the Centre for Clinical Trials of the Chinese University of Hong Kong, ISSN 0161-6420/09/$–see front matter doi:10.1016/j.ophtha.2008.12.054
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Ophthalmology Volume 116, Number 4, April 2009 which has been recognized by the International Committee of Medical Journal Editors for clinical trial registration (http:// 137.189.150.15/registry/publictriallist.php;date of access and registration: September 7, 2005). Informed consents were obtained from all patients before recruitment. Patients with medically uncontrolled CACG and cataract, and fulfilling the recruitment criteria in Table 1 (available at http:// aaojournal.org), were recruited. Only 1 eye from each patient could be recruited. If both eyes of 1 patient had coexisting CACG and cataract, the eye with the more mature cataract was included in the study. If both eyes had equally mature cataract, 1 eye was randomly selected for study using a random number table. Preoperative IOP (median of 3 Goldmann applanation readings taken on different days), number of IOP-lowering drugs, best corrected visual acuity (BCVA) by Snellen chart and converted to logarithm of the minimum angle of resolution (LogMAR) visual acuity, angle grading by indentation gonioscopy, vertical cup-todisk ratio (VCDR), and optic nerve head assessment by expert observer at the slit lamp using a 90D hand-held lens and with optic disc photography, and visual field (static automated white-onwhite threshold perimetry program 24- 2, SITA-standard, model 750, Humphrey Instruments, Dublin, CA) were documented for the study eye. The VCDR was taken to be the longest vertical cup diameter divided by the longest vertical disc diameter. The study eye was then randomized into 1 of 2 treatment groups using a random number table: phaco alone or combined phacotrabeculectomy with adjunctive mitomycin C chemotherapy. The surgical interventions in the 2 treatment groups are summarized in Table 2 (available at http://aaojournal.org). The procedures were performed under topical, retrobulbar, or peribulbar anesthesia, depending on patients’ or surgeons’ preferences, or clinical indications. Adjunctive mitomycin C was applied to the scleral surface before scleral incision (0.4 mg/ml). Standard application duration was 2 minutes, which was increased to 3 minutes if any of the following criteria were present: (a) extensive uveal manipulation anticipated, for example, significant posterior synechiae present; (b) young patient (age ⬍40 years); (c) previous failed trabeculectomy or phacotrabeculectomy in the fellow eye; and (d) prolonged use of topical IOP-lowering drugs, with conjunctival changes on slit-lamp examination. Postoperatively, study visits were scheduled at 1 day, 1 week, 1 month, 3 months, and then every 3 months for a minimum of 2 years, with documentation of IOP (median of 3 Goldmann applanation readings), number of IOP-lowering drugs required, BCVA, angle status by indentation gonioscopy, complications, additional interventions required to maintain filtration or handle complications, and VCDR. Observers were not masked from the surgery performed. Optic disc photography and visual field by Humphrey automated perimetry were repeated at annual intervals. Postoperatively, only eyes with an untreated IOP ⬎21 mmHg were resumed on IOP-lowering drugs to maintain an IOP of 21 mmHg or less. Glaucoma drugs were added in the following order: (1) beta-blockers, (2) prostaglandin analogues, (3) carbonic anhydrase inhibitors, (4) pilocarpine, (5) adrenergic agonists. Additional clinic visits and investigations were to be scheduled as and when required. All these were recorded in the datasheet.
served at 2 or more separate follow-up visits; (2) appearance of new splinter hemorrhage; (3) appearance of new or extension of old neuroretinal rim notching observed at 2 or more separate clinic visits; (4) appearance of new or extension of old nerve fiber layer defects observed at 2 or more separate clinic visits. Progression based on changes in Humphrey25 automated perimetry was as per published standard: defect deepened or enlarged if 2 or more points within or adjacent to an existing scotoma have worsened by at least 10 dB; all progression required confirmation on at least 1 subsequent field and clinical correlation with no other explanation for deterioration.
Outcome Measures
Statistical Methods
The primary outcome measures were IOP and the number of IOP-lowering drugs. Secondary outcome measures included BCVA, changes in optic nerve morphology and visual field, surgical complications, and need for additional surgical interventions. Progression based on changes in glaucomatous optic nerve head morphology was confirmed if 1 or more of the following criteria was fulfilled: (1) increase in VCDR of 0.1 or more ob-
All statistics were calculated using the Statistical Package for the Social Sciences 15.0 for Windows (SPSS Inc., Chicago, IL). Continuous data were expressed in mean ⫾ standard deviation and compared using the Student t test or Mann–Whitney U test as appropriate. Categoric data were expressed in percentages and compared using the chi-square test. A P value of ⬍0.05 was considered statistically significant.
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Indications for Additional Surgical Intervention in the Postoperative Period In both treatment groups, Yag capsulotomy was indicated if there was significant posterior capsular opacification causing a deterioration in BCVA. In the “phaco alone” group, secondary trabeculectomy was indicated if IOP increased to greater than 21 mmHg with 3 or more topical glaucoma drugs at more than 1 follow-up visit. In the combined phacotrabeculectomy group, suturing for conjunctival wound leak was performed if the leak did not stop after aqueous suppression and eye patching for 3 days. Laser suturelysis was indicated if IOP increased to greater than 21 mmHg from 1 week to 1 month after surgery without IOP-lowering drugs, whereas subconjunctival 5-fluorouracil injection was indicated if there was significant and persistent conjunctival congestion despite maximal topical steroid treatment in the postoperative period. Intervention for overdrainage was indicated if hypotony (IOP ⬍6 mmHg) persisted for more than 2 months in an eye with good visual prognosis or if complications (e.g., hypotony maculopathy) were detected. Interventions for overdrainage include conservative measures such as bleb compression and aqueous suppressants, and surgical procedures such as intra-bleb autologous blood injection, conjunctival suturing, or open revision of trabeculectomy, depending on the severity of hypotony and its complications.
Sample Size Calculation Sample size calculation was performed with the principal investigator’s own unpublished data (2001–2002) from a pilot study. The mean preoperative IOP (⫾ standard deviation) was 27.4 (⫾8.5) mmHg in the medically uncontrolled CACG eyes with cataract in the pilot study. The aim of the surgery was to achieve a “normal” untreated IOP, which was defined as 21 mmHg or less. Thus, the required reduction in IOP was 6.4 mmHg. On the basis of these data, and assuming an alpha of 0.05 and a power of 80%, to prove that the 2 interventions were equivalent in decreasing the IOP to the normal level, a minimum of 23 patients would be required in each arm.
Tham et al 䡠 Phaco versus Phacotrabeculectomy in Chronic Angle Closure Glaucoma Table 3. Patient Demographics of the Two Treatment Groups Combined Phacotrabeculectomy with Adjunctive Mitomycin C Group P Value
Phaco Group No. of eyes (No. of patients) Mean age ⫾ SD (yrs) Male : female ratio Left eye : right eye ratio
27 (27) 70.3⫾7.4 yrs (range, 52–83 yrs) 9 : 18 15 : 12
24 (24) 70.4⫾9.0 yrs (range, 55–91 yrs) 6 : 18 10 : 14
0.99* 0.51† 0.32†
SD ⫽ standard deviation. *Student t test. † Chi-square test.
Results Patient Demographics and Preoperative Clinical Status During the study recruitment period from March 2002 to October 2007, 51 medically uncontrolled CACG eyes with coexisting cataract of 51 patients were recruited. Of these 51 eyes, 27 were randomized into the “phaco alone” treatment group and 24 were randomized into the “combined phacotrabeculectomy with adjunctive mitomycin C chemotherapy” treatment group. Table 3 summarizes the patient demographics. There were more female than male patients in both treatment groups, but the difference between the groups did not reach statistical significance (P ⫽ 0.06). Table 4 summarizes the preoperative clinical status of the 2 treatment groups.
Surgical Procedures and Follow-up The surgical procedures were performed by 9 experienced glaucoma surgeons in 3 ophthalmic centers (Hong Kong Eye Hospital, United Christian Hospital, and Prince of Wales Hospital). In both treatment groups, all surgical procedures were performed under local anesthesia, including topical, retrobulbar, peribulbar, and subtenon anesthesias. Within the combined surgery group, 2 CACG eyes had mitomycin C application for 2 minutes, and 22 eyes had mitomycin C application for 3 minutes, in accordance with criteria in Table 2 (available at http://aaojournal.org).
Mean follow-up durations ⫾1 standard deviation were 33.4⫾ 10.5 months (range, 24.0 –53.5 months) in the “phaco alone” group and 37.6⫾10.3 months (range, 24.0 – 69.4 months) in the “combined phacotrabeculectomy with adjunctive mitomycin C chemotherapy” group (P ⫽ 0.2). In this article, the outcome measures up to the 24-month follow-up are reported.
Main Outcome Measures Figure 1 compares the IOP profiles of the 2 groups of patients. The IOP at various time points of follow-up for the 2 groups of patients is summarized in Table 5 (available at http://aaojournal.org). There were no statistically significant differences (P⬎0.05) in mean IOP between the 2 treatment groups preoperatively and postoperatively, except at 3 months (P ⫽ 0.01), 15 months (P ⫽ 0.02), and 18 months (P ⫽ 0.01). Within both treatment groups, the mean postoperative IOPs at all postoperative time points up to 24 months were statistically significantly lower (P⬍0.001) than the mean preoperative IOPs. No eyes in either treatment group had IOP of 6 mmHg or less at any postoperative time points. Table 6 (available at http://aaojournal.org) summarizes the mean number of topical glaucoma drugs at various time points of follow-up for the 2 groups of patients. Figure 2 compares the mean number of topical glaucoma drugs in the 2 groups of patients. There was no statistically significant difference (P ⫽ 0.45) in the mean preoperative number of glaucoma drugs between the 2 treatment groups. The mean numbers of topical glaucoma drugs required in the “combined phacotrabeculectomy with adjunctive
Table 4. Preoperative Clinical Status of the Two Treatment Groups Phaco Group
Combined Phacotrabeculectomy with Adjunctive Mitomycin C Group
Mean preoperative IOP ⫾ SD (mmHg) 24.4⫾6.1 mmHg (range, 14.0–38.0 mmHg) 23.8⫾4.3 mmHg (range, 15.0–32.0 mmHg) Mean No. of preoperative IOP-lowering 3.3⫾1.1 (range, 2–5) 3.1⫾0.9 (range, 2–5) drugs ⫾ SD Mean preoperative BCVA ⫾ SD (LogMar) 0.8⫾0.7 (range, 0.4–3.0) 0.7⫾0.4 (range, 0.4–1.6) Extent of synechial angle closure ⫾ SD 275.0⫾54.1 degrees (range, 180–360 degrees) 256.9⫾72.0 degrees (range, 180–360 degrees) (degrees) Mean VCDR ⫾ SD 0.8⫾0.2 (range, 0.3–0.9) 0.7⫾0.2 (range, 0.4–1.0) Automated perimetry: Mean MD ⫾ SD (db) ⫺17.5⫾11.4 db (range, ⫺2.1 to ⫺31.3 db) ⫺16.6⫾11.2 db (range, ⫺2.2 to ⫺32.1 db) Automated perimetry: Mean PSD ⫾ SD (db) 5.1⫾3.4 db (range, 1.7–14.7 db) 4.8⫾3.3 db (range 1.5–12.4 db) Eyes with history of acute angle closure 7/27 6/24 attack
P Value 0.72* 0.45* 0.56* 0.31* 0.34* 0.79* 0.74* 0.94†
BCVA ⫽ best corrected visual acuity; db ⫽ decibel; IOP ⫽ intraocular pressure; LogMAR ⫽ logarithm of the minimum angle of resolution; MD ⫽ mean deviation; PSD ⫽ pattern standard deviation; SD ⫽ standard deviation; VCDR ⫽ vertical cup-to-disk ratio. *Student t test. † Chi-square test.
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Figure 1. Intraocular pressure profiles of phaco and phacotrabeculectomy groups.
mitomycin C chemotherapy” treatment group were statistically significantly lower (P⬍0.001) than the mean numbers of topical glaucoma drugs in the “phaco alone” group at all postoperative time points. None of the study patients required systemic IOPlowering drugs to control IOP either preoperatively or postoperatively. During the 24-month postoperative follow-up period, the mean postoperative number of topical glaucoma drugs in the “combined phaco-trabeculectomy with adjunctive mitomycin C chemotherapy” treatment group were on average 1.25 lower than the mean postoperative number of topical glaucoma drugs in the “phaco alone” group (P⬍0.001). At 24 months, 7 of 27 (25.9%) “phaco alone” eyes did not require any glaucoma drugs, whereas 17 of 24 (70.8%) combined phacotrabeculectomy eyes did not require any glaucoma drugs. In both treatment groups, the mean postoperative number of topical glaucoma drugs at all postoperative time points was statistically significantly lower (P⬍0.001) than the mean preoperative number of topical glaucoma drugs. Table 7 summarizes the proportion of CACG cases with controlled IOP after the 2 treatments. By applying the same definition of “medically controlled” as applied in our previous study,24 both treatments achieved more than 90% of IOP control at both 12 and 24 months after surgery, and there was no statistically significant difference between the 2 treatments at both time points.
In the “phaco alone” group, 1 eye had worse LogMAR BCVA at 2 years compared with before surgery. This eye had progression of age-related macular degeneration with extension of macular scarring and did not have any surgical complications. In the combined surgery group, 4 eyes had worse LogMAR BCVA at 2 years compared with before surgery. All 4 eyes had very advanced glaucomatous optic neuropathy and visual field loss before surgery. Two eyes had immediate deterioration in visual acuity after surgery (“wipe-out” phenomenon). These 2 eyes did not have any intraoperative surgical complications. The other 2 eyes had poor IOP control and gradual progression of glaucomatous optic neuropathy during the 2 years of follow-up. One of these 2 eyes had needling revision of the trabeculectomy site with adjunctive 5-fluorouracil chemotherapy performed twice, whereas the other eye had repeated subconjunctival injections of 5-fluorouracil (5 mg) in the early postoperative period and needling revision with adjunctive 5-fluorouracil chemotherapy performed once. There were no statistically significant differences in mean VCDR between the 2 groups preoperatively and at the 12- and 24-month follow-ups. Within the “phaco alone” group, there were no statistically significant changes in mean VCDR at both the 12and 24-month follow-ups compared with the preoperative status. Within the combined surgery group, there were statistically significant increases in VCDR at both the 12-month (P ⫽ 0.001) and 24-month (P⬍0.001) follow-ups, compared with the preoperative status. On the basis of our definition of progression of glaucomatous optic neuropathy outlined above, none of the 27 CACG eyes (0%) in the “phaco alone” group demonstrated progression during the 2-year follow-up period, whereas 4 of the 24 CACG eyes (16.7%) in the “combined phacotrabeculectomy with adjunctive mitomycin C chemotherapy” treatment group demonstrated progression during the 2-year follow-up period (P ⫽ 0.03, 2 test). There were no statistically significant differences in mean pattern standard deviation on Humphrey automated perimetry between the 2 groups preoperatively and at the 12- and 24-month follow-ups. Within each treatment group, there were no statisti-
Secondary Outcome Measures Table 8 summarizes the mean LogMAR BCVA of the 2 treatment groups at various time points. There were no statistically significant differences in mean LogMAR BCVA between the 2 groups preoperatively and at the 12- and 24-month follow-ups. Within the “phaco alone” group, there was statistically significant (P ⫽ 0.001) improvement in mean LogMAR BCVA at both the 12- and 24month follow-ups compared with the preoperative status. Within the “combined phacotrabeculectomy with adjunctive mitomycin C chemotherapy” treatment group, the mean LogMAR BCVA at the 12- and 24-month follow-ups was better than the preoperative mean LogMAR BCVA, but the differences did not reach statistical significance (P ⫽ 0.24 for 12 months, and P ⫽ 0.68 for 24 months).
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Figure 2. Profiles of requirements for topical glaucoma drugs in the 2 treatment groups.
Tham et al 䡠 Phaco versus Phacotrabeculectomy in Chronic Angle Closure Glaucoma Table 7. Proportion of Chronic Angle Closure Glaucoma Cases with Controlled Intraocular Pressure after the Two Treatments No. of CACG Eyes with IOP Controlled Phaco Group Combined Phacotrabeculectomy with by Medications* (Percentages) (n ⴝ 27) Adjunctive Mitomycin C Group (n ⴝ 24) P Value† Preoperative 12 mos after surgery 24 mos after surgery
0 (0%) 25 (92.6%) 25 (92.6%)
0 (0%) 24 (100%) 22 (91.7%)
0.17 0.90
CACG ⫽ chronic angle closure glaucoma; IOP ⫽ intraocular pressure. *Based on the definitions in this study. † Chi-square test.
cally significant changes in mean pattern standard deviation at both the 12- and 24-month follow-ups compared with the preoperative status. On the basis of our definition of progression of glaucomatous visual field outlined previously, 11 of the 27 CACG eyes (40.7%) in the “phaco alone” group demonstrated progression during the 2-year follow-up period, whereas 9 of the 24 CACG eyes (37.5%) in the “combined phacotrabeculectomy with adjunctive mitomycin C chemotherapy” treatment group demonstrated progression during the 2-year follow-up period (P ⫽ 0.81, 2 test). There was no statistically significant difference between the 2 treatment groups in the number of intraoperative complications (P ⫽ 0.74). The “combined phacotrabeculectomy with adjunctive mitomycin C chemotherapy” treatment group had significantly more postoperative complications (8 complications) than the “phaco alone” group (0 complications) (P ⫽ 0.001). There were no statistically significant differences between the 2 treatment groups in the number of additional surgical interventions required to control IOP or to manage complications (P ⫽ 0.21 and 0.13, respectively). Four eyes (14.8%) in the “phaco alone” group subsequently required trabeculectomy to control IOP during the 24month follow-up. All 4 cases did not have surgical complications and had IOP controlled up to 24 months after the initial phacoemulsification. Details of these complications, their management and outcomes, and the additional surgical interventions will be presented in a subsequent publication.
Discussion Two sister randomized controlled clinic trials were undertaken in Hong Kong to compare the efficacy in IOP control of cataract extraction alone by phacoemulsification versus combined phacotrabeculectomy with adjunctive mitomycin C chemotherapy in CACG eyes with coexisting cataract.
The other study24 focused on the subgroup of CACG eyes with medically controlled IOP before surgery, whereas this study focused on those CACG eyes with medically uncontrolled IOP before surgery. Table 9 (available at http:// aaojournal.org) summarizes the key difference in recruitment criteria and the clinical outcomes of the 2 randomized controlled trials. From both trials, it is clear that phacoemulsification alone is effective in improving IOP control, both in terms of decreasing IOP and reducing the requirement for glaucoma drugs, in CACG eyes with cataract, whether the preoperative IOP is medically controlled or not. Combined phacotrabeculectomy resulted in lower mean IOP than phaco alone at all time points up to 24 months after surgery, whether the preoperative IOP was controlled or not. However, this difference reached statistical significance in only a minority of time points. Combined phacotrabeculectomy resulted in the requirement of significantly fewer glaucoma drugs than phaco alone at all time points up to 24 months after surgery, whether the preoperative IOP was controlled (average 0.80 fewer drugs over 24 months) or uncontrolled (average 1.25 fewer drugs over 24 months). When the definition of “medically controlled” from our previous publication24 was used, there was no statistically significant difference between the 2 treatments in the proportion of cases that became “medically controlled” at both 12 and 24 months after surgery (Table 7). On the basis of these findings, combined phacotrabeculectomy seemed to be more effective than phaco alone in controlling IOP in CACG eyes with cataract, but the difference appeared marginal and was mainly in a lower requirement for glaucoma drugs. Using an average of 1 less glau-
Table 8. Mean Logarithm of the Minimum Angle of Resolution Best Corrected Visual Acuity of the Two Treatment Groups at Various Time Points LogMAR BCVA
Phaco Group
Mean preoperative ⫾ SD 0.8⫾0.7 (range, 0.4–3.0) Mean postoperative at 12 mos ⫾ SD 0.6⫾0.7 (range, 0.0–3.0) Mean postoperative at 24 mos ⫾ SD 0.6⫾0.7 (range, 0.0–3.0)
Combined Phacotrabeculectomy with Adjunctive Mitomycin C Group P Value* 0.7⫾0.4 (range, 0.4–1.6) 0.5⫾0.6 (range, 0.1–3.0) 0.6⫾0.8 (range, 0.2–3.0)
0.56 0.84 0.77
BCVA ⫽ best corrected visual acuity; LogMAR ⫽ logarithm of the minimum angle of resolution; SD ⫽ standard deviation. *Student t test.
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Ophthalmology Volume 116, Number 4, April 2009 coma drug during a 24-month period may mean less adverse drug effects and convenience for the patients, improved compliance with the remaining drugs, and lower cost to patients or society; however, there was a price to pay for the mean difference of approximately 1 glaucoma drug between the 2 treatments, and this included significantly more postoperative complications in the combined phacotrabeculectomy group in both studies and significantly more cases with progression of glaucomatous optic neuropathy in the combined phacotrabeculectomy group in the CACG eyes with uncontrolled preoperative IOP (current study). These differences were, however, not reflected in the BCVA or the performance (pattern standard deviation) in automated perimetry. A detailed analysis of the functional outcomes and the impact on the patients’ quality of life will be presented in a subsequent publication. There are inherent weaknesses in our study design. Although the phacoemulsification procedure was well standardized, there were bound to be small individual variations in surgical techniques in trabeculectomy between the surgeons. Furthermore, this study was powered to study the differences in IOP control between the 2 treatment groups. This study may not have sufficient power (sample size) and follow-up duration to look at other parameters, such as complications and glaucomatous progression. The results from these 2 studies are not applicable to those CACG cases with no coexisting cataract. To respect patients’ and surgeons’ preference, we were not able to standardize the type of anesthesia, which may have an influence on the clinical outcome. For example, subtenon or peribulbar anesthesia may be more likely to influence bleb formation than general anesthesia. Retrobulbar anesthesia may affect the optic nerve and the visual field in the final stages of glaucoma. On the basis of the data from these 2 studies, phacoemulsification alone is a viable surgical alternative to combined phacotrabeculectomy in CACG eyes with coexisting cataract, whether the preoperative IOP is medically controlled or not. The additional postoperative complications in the combined surgery group may not be justified by the small additional lowering in the requirement of glaucoma drugs. Although a small proportion (14.8% in the current study with uncontrolled preoperative IOP and 2.9% in the previous publication24 with controlled preoperative IOP) of phacotreated CACG eyes require a subsequent trabeculectomy for IOP control, there is no available evidence to suggest that these eyes will do worse than eyes receiving combined surgery, in terms of long-term visual outcomes, IOP control, or complications.
References 1. Lai JS, Tham CC, Lam DS. Incisional surgery for angle closure glaucoma. Semin Ophthalmol 2002;17:92–9. 2. Bellucci R, Perfetti S, Babighian S, et al. Filtration and complications after trabeculectomy and after phaco-trabeculectomy. Acta Ophthalmol Scand Suppl 1997;(224):44 –5. 3. Tham CC, Lai JS, Poon AS, et al. Results of trabeculectomy with adjunctive intraoperative mitomycin C in Chinese patients with glaucoma. Ophthalmic Surg Lasers Imaging 2006; 37:33– 41.
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4. Foster PJ. The epidemiology of primary angle closure and associated glaucomatous optic neuropathy. Semin Ophthalmol 2002;17:50 – 8. 5. 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: 633– 42. 6. Lowe RF. Causes of shallow anterior chamber in primary angle-closure glaucoma: ultrasonic biometry of normal and angle-closure glaucoma eyes. Am J Ophthalmol 1969;67: 87–93. 7. Lowe RF. Aetiology of the anatomical basis for primary angle-closure glaucoma: biometrical comparisons between normal eyes and eyes with primary angle-closure glaucoma. Br J Ophthalmol 1970;54:161–9. 8. Markowitz SN, Morin JD. Angle-closure glaucoma: relation between lens thickness, anterior chamber depth and age. Can J Ophthalmol 1984;19:300 –2. 9. Tornquist R. Chamber depth in primary acute glaucoma. Br J Ophthalmol 1956;40:421–9. 10. Wojciechowski R, Congdon N, Anninger W, Teo Broman A. Age, gender, biometry, refractive error, and the anterior chamber angle among Alaskan Eskimos. Ophthalmology 2003;110: 365–75. 11. Di Staso S, Sabetti L, Taverniti L, et al. Phacoemulsification and intraocular lens implant in eyes with primary angleclosure glaucoma: our experience. Acta Ophthalmol Scand Suppl 2002;236:17– 8. 12. Hayashi K, Hayashi H, Nakao F, Hayashi F. Changes in anterior chamber angle width and depth after intraocular lens implantation in eyes with glaucoma. Ophthalmology 2000; 107:698 –703. 13. Tran HV, Liebmann JM, Ritch R. Iridociliary apposition in plateau iris syndrome persists after cataract extraction. Am J Ophthalmol 2003;135:40 –3. 14. Yang CH, Hung PT. Intraocular lens position and anterior chamber angle changes after cataract extraction in eyes with primary angle-closure glaucoma. J Cataract Refract Surg 1997;23:1109 –13. 15. Acton J, Salmon JF, Scholtz R. Extracapsular cataract extraction with posterior chamber lens implantation in primary angle-closure glaucoma. J Cataract Refract Surg 1997;23:930 – 4. 16. Greve EL. Primary angle closure glaucoma: extracapsular cataract extraction or filtering procedure? Int Ophthalmol 1988;12:157– 62. 17. Gunning FP, Greve EL. Uncontrolled primary angle closure glaucoma: results of early intercapsular cataract extraction and posterior chamber lens implantation. Int Ophthalmol 1991;15: 237– 47. 18. Gunning FP, Greve EL. Lens extraction for uncontrolled angleclosure glaucoma: long-term follow-up. J Cataract Refract Surg 1998;24:1347–56. 19. Wishart PK, Atkinson PL. Extracapsular cataract extraction and posterior chamber lens implantation in patients with primary chronic angle-closure glaucoma: effect on intraocular pressure control. Eye 1989;3:706 –12. 20. Ge J, Guo Y, Liu Y, et al. New management of angle-closure glaucoma by phacoemulsification with foldable posterior chamber intraocular lens implantation. Yan Ke Xue Bao 2000; 16:22– 8. 21. Hayashi K, Hayashi H, Nakao F, Hayashi F. Effect of cataract surgery on intraocular pressure control in glaucoma patients. J Cataract Refract Surg 2001;27:1779 – 86. 22. Kubota T, Toguri I, Onizuka N, Matsuura T. Phacoemulsification and intraocular lens implantation for angle closure
Tham et al 䡠 Phaco versus Phacotrabeculectomy in Chronic Angle Closure Glaucoma glaucoma after the relief of pupillary block. Ophthalmologica 2003;217:325– 8. 23. Lai JS, Tham CC, Chan JC. 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: 47–52.
24. Tham CC, Kwong YY, Leung DY, et al. Phacoemulsification versus combined phacotrabeculectomy in medically controlled chronic angle closure glaucoma with cataract. Ophthalmology 2008;115:2167–73. 25. Anderson DR, Chauhan B, Johnson C, et al. Criteria for progression of glaucoma in clinical management and in outcome studies. Am J Ophthalmol 2000;130:827–9.
Footnotes and Financial Disclosures Originally received: August 12, 2008. Final revision: December 12, 2008. Accepted: December 19, 2008. Available online: February 25, 2009.
Supported by a Direct Grant for Research from the Chinese University of Hong Kong 2004 –2005. The funding organization had no role in the design or conduct of this research. Manuscript no. 2008-965.
1
Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China. 2
Hong Kong Eye Hospital, Kowloon, Hong Kong SAR, People’s Republic of China. 3
Prince of Wales Hospital, Shatin, N.T., Hong Kong SAR, People’s Republic of China. 4
Department of Ophthalmology, United Christian Hospital, Kowloon, Hong Kong SAR, People’s Republic of China.
Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Correspondence: Clement C. Y. Tham, FRCS, Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong Eye Hospital, 147K Argyle Street, Kowloon, Hong Kong. E-mail: clemtham@hkstar. com.
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Ophthalmology Volume 116, Number 4, April 2009 Table 1. Recruitment Criteria Diagnostic criteria for medically controlled CACG:
Diagnostic criteria for cataract: Inclusion criteria: Exclusion criteria:
At least 180 degrees of angle closure obliterating pigmented part of trabecular meshwork, whether synechial or appositional, segmented or continuous, in the presence of a patent peripheral iridotomy; requiring IOP-lowering medications, or IOP ⬎21 mmHg without IOP-lowering medications; visual field loss compatible with glaucoma* and/or glaucomatous optic disc changes Definition of “medically uncontrolled”: IOP ⬎21 mmHg despite maximally tolerated medications or requiring ⬎3 topical drugs for IOP control (combination drugs counted as 2 drugs) Presence of nucleus sclerosis, cortical cataract, or subcapsular cataract; visual acuity of 20/50 or worse, and affecting activities of daily living Eyes with CACG and coexisting cataract as defined above Patient able and willing to give informed consent to phacoemulsification or combined phacotrabeculectomy, before randomization Single functional eye; patients refusing either cataract extraction or trabeculectomy; previous intraocular surgery, with the exception of laser peripheral iridotomy and argon laser peripheral iridoplasty
CACG ⫽ chronic angle closure glaucoma; IOP ⫽ intraocular pressure. *Minimal criteria for glaucomatous visual field defect as per published standard:25 glaucoma hemifield test outside normal limits, pattern standard deviation with a P value of ⬍5%, or a cluster of ⱖ3 points in the pattern deviation plot in a single hemifield (superior or inferior) with P value of ⬍5%, one of which must have a P value of ⬍1%. Any one of the preceding criteria, if repeatable, was considered sufficient evidence of a glaucomatous visual field defect.
Table 2. Interventions in the Two Treatment Groups after Randomization Phacoemulsification Group
Combined Phacotrabeculectomy Group
Any topical pilocarpine was stopped for 1 wk before phaco (other eye medications continued up to and beyond phaco). Corneal incisions were used to preserve conjunctiva for future filtration surgery. Posterior synechialysis, pupil stretching by Kuglen hooks, and the use of iris hooks to maintain an enlarged pupil were used where indicated. Foldable and injectable intraocular lenses were implanted into the capsular bag whenever possible. A complete evacuation of viscoelastic agent was attempted in every case at the end of surgery. Topical Prednisol 1% and topical chloramphenicol were given postoperatively. Frequency and duration were dictated by clinical needs. Postoperatively, 1 stat dose of 250 mg oral acetazolamide was given as prophylaxis against IOP spike. Additional oral acetazolamide could be given to treat IOP spike as indicated. Postoperatively, any glaucoma eyedrops were tailed down if the mean IOPs at 2 consecutive visits were ⱕ21 mmHg. The order of stopping drugs was the reverse of the order of resuming drugs, i.e., adrenergic agonists first, followed by pilocarpine, carbonic anhydrase inhibitors, prostaglandin analogues, and beta-blockers.
Any topical pilocarpine was stopped for 1 wk before phacotrabeculectomy (other eye medications continued up to day of phacotrabeculectomy). Either 1- or 2-site phacotrabeculectomy could be performed, depending on surgeon’s preference. Adjunctive MMC was applied to the scleral surface before scleral incision (0.4 mg/ml). Standard application duration was 2 min, which was increased to 3 min if any of the following criteria were present: Extensive uveal manipulation anticipated, e.g., significant posterior synechiae present Young patient (age ⬍40 yrs) Previous failed trabeculectomy or phacotrabeculectomy in fellow eye Prolonged use of topical IOP-lowering drugs, with conjunctival changes on slit-lamp examination Posterior synechialysis, pupil stretching by Kuglen hooks, and the use of iris hooks to maintain an enlarged pupil were used where indicated. Foldable and injectable intraocular lenses were implanted into the capsular bag whenever possible. A complete evacuation of viscoelastic agent was attempted in every case at the end of surgery. Topical Prednisol 1% and topical chloramphenicol were given postoperatively. Frequency and duration were dictated by clinical needs. Postoperatively, laser suturelysis was performed if there was no bleb and IOP increased ⬎21 mmHg.
IOP ⫽ intraocular pressure; MMC ⫽ mitomycin C.
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Tham et al 䡠 Phaco versus Phacotrabeculectomy in Chronic Angle Closure Glaucoma Table 5. Intraocular Pressure at Various Time Points of Follow-up for the Two Groups of Study Patients Phaco Group Mean preoperative IOP ⫾ SD (mmHg) Mean 1-mo postoperative IOP ⫾ SD (mmHg) Mean 3-mo postoperative IOP ⫾ SD (mmHg) Mean 6-mo postoperative IOP ⫾ SD (mmHg) Mean 9-mo postoperative IOP ⫾ SD (mmHg) Mean 12-mo postoperative IOP ⫾ SD (mmHg) Mean 15-mo postoperative IOP ⫾ SD (mmHg) Mean 18-mo postoperative IOP ⫾ SD (mmHg) Mean 21-mo postoperative IOP ⫾ SD (mmHg) Mean 24-mo postoperative IOP ⫾ SD (mmHg)
Combined Phacotrabeculectomy with Difference in Mean IOP Adjunctive Mitomycin C Group between 2 Groups
P Value*
24.4⫾6.1 (range, 14.0–38.0) 15.7⫾3.9 (range, 8.0–22.0)
23.8⫾4.3 (range, 15.0–32.0) 13.7⫾3.4 (range, 9.0–21.0)
0.6 mmHg 2.0 mmHg
0.72 0.05
17.0⫾3.3 (range, 12.0–25.0)
14.0⫾4.2 (range, 8.0–24.0)
3.0 mmHg
0.01
16.3⫾3.5 (range, 10.0–25.0)
14.8⫾4.7 (range, 9.0–26.0)
1.5 mmHg
0.19
15.9⫾3.3 (range, 10.0–24.0)
14.6⫾3.3 (range, 10.0–20.0)
1.2 mmHg
0.20
15.5⫾3.2 (range, 10.0–22.0)
14.0⫾4.4 (range 7.0–22.0)
1.5 mmHg
0.16
15.4⫾3.2 (range, 10.0–22.0)
13.2⫾3.2 (range, 10.0–21.0)
2.2 mmHg
0.02
15.9⫾3.0 (range, 11.0–22.0)
13.6⫾3.4 (range 10.0–21.0)
2.3 mmHg
0.01
16.1⫾3.6 (range, 11.0–27.0)
14.1⫾4.2 (range 9.0–25.0)
2.0 mmHg
0.07
16.1⫾4.1 (range, 9.0–27.0)
14.1⫾3.7 (range 9.0–22.0)
2.0 mmHg
0.08
IOP ⫽ intraocular pressure; SD ⫽ standard deviation. *Student t test.
Table 6. Number of Topical Glaucoma Drugs Required at Various Time Points of Follow-up for the Two Groups of Study Patients
Mean preoperative No. of glaucoma drugs ⫾ SD Mean 3-mo postoperative No. of glaucoma drugs ⫾ SD Mean 6-mo postoperative No. of glaucoma drugs ⫾ SD Mean 9-mo postoperative No. of glaucoma drugs ⫾ SD Mean 12-mo postoperative No. of glaucoma drugs ⫾ SD Mean 15-mo postoperative No. of glaucoma drugs ⫾ SD Mean 18-mo postoperative No. of glaucoma drugs ⫾ SD Mean 21-mo postoperative No. of glaucoma drugs ⫾ SD Mean 24-mo postoperative No. of glaucoma drugs ⫾ SD
Phaco Group
Combined Phacotrabeculectomy with Adjunctive Mitomycin C Group
Difference in Mean No. of Topical Glaucoma Drugs between the 2 Groups
P Value*
3.3⫾1.1 (range, 2–5)
3.1⫾0.9 (range, 2–5)
0.2
0.45
1.5⫾1.2 (range, 0–3)
0.3⫾0.8 (range, 0–3)
1.2
⬍0.001
1.5⫾1.3 (range, 0–4)
0.3⫾0.7 (range, 0–3)
1.2
⬍0.001
1.5⫾1.4 (range, 0–4)
0.4⫾0.9 (range, 0–3)
1.1
⬍0.001
1.5⫾1.4 (range, 0–4)
0.3⫾0.6 (range, 0–2)
1.2
⬍0.001
1.6⫾1.4 (range, 0–4)
0.3⫾0.5 (range, 0–2)
1.3
⬍0.001
1.6⫾1.4 (range, 0–4)
0.3⫾0.6 (range, 0–2)
1.3
⬍0.001
1.7⫾1.4 (range, 0–4)
0.3⫾0.8 (range, 0–3)
1.4
⬍0.001
1.7⫾1.3 (range, 0–4)
0.5⫾1.0 (range, 0–4)
1.2
⬍0.001
SD ⫽ standard deviation. *Student t test.
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Ophthalmology Volume 116, Number 4, April 2009 Table 9. Summary of Recruitment Criteria and Clinical Outcomes of Two Randomized Controlled Trials on Chronic Angle Closure Glaucoma with Coexisting Cataract Previous RCT on Medically Controlled CACG with Cataract24
Current RCT on Medically Uncontrolled CACG with Cataract
Key difference in recruitment criteria
“Medically controlled” defined as IOP ⱕ21 mmHg, with ⱕ3 topical drugs
IOP
No significant differences (P⬎0.05) in mean IOP between the 2 treatment groups preoperatively and postoperatively, except at 1 mo (P ⫽ 0.001) and 3 mos (P ⫽ 0.008). The “combined phacotrabeculectomy” group required statistically significantly fewer drugs (P⬍0.001) than the “phaco alone” group at all postoperative time points. Over the 24-mo follow-up period, the mean postoperative No. of topical glaucoma drugs in the “combined phacotrabeculectomy” group were on average 0.80 lower than in the “phaco alone” group (P⬍0.001) No statistically significant difference between 2 treatment groups No statistically significant difference between 2 treatment groups Significantly more complications in the combined phacotrabeculectomy group No statistically significant difference between 2 treatment groups No statistically significant difference between 2 treatment groups No statistically significant difference between 2 treatment groups
“Medically uncontrolled” defined as IOP ⬎21 mmHg despite maximally tolerated medications or requiring ⬎3 topical drugs for IOP control No significant differences (P⬎0.05) in mean IOP between the 2 treatment groups preoperatively and postoperatively, except at 3 mos (P ⫽ 0.01), 15 mos (P ⫽ 0.02), and 18 mos (P ⫽ 0.01). The “combined phacotrabeculectomy” group required statistically significantly fewer drugs (P⬍0.001) than the “phaco alone” group at all postoperative time points. Over the 24-mo follow-up period, the mean postoperative No. of topical glaucoma drugs in the “combined phacotrabeculectomy” group were on average 1.25 lower than in the “phaco alone” group (P⬍0.001)
Requirement for topical glaucoma drugs
Mean LogMAR BCVA before surgery and at 12 and 24 mos after surgery Intraoperative complications Postoperative complications Additional surgical interventions Progression of GON Progression of GVFL
No statistically significant difference between 2 treatment groups No statistically significant difference between 2 treatment groups Significantly more complications in the combined phacotrabeculectomy group No statistically significant difference between 2 treatment groups Significantly more cases in the combined phacotrabeculectomy group No statistically significant difference between 2 treatment groups
BCVA ⫽ best corrected visual acuity; CACG ⫽ chronic angle closure glaucoma; GON ⫽ glaucomatous optic neuropathy; GVFL ⫽ glaucomatous visual field loss; IOP ⫽ intraocular pressure; LogMAR ⫽ logarithm of the minimum angle of resolution; RCT ⫽ randomized controlled trial.
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The prevalence of chronic angle closure glaucoma (CACG) increases with age, and CACG therefore frequently coexists with cataract. In such patients, it is common practice to perform combined cataract extraction and trabeculectomy (phacotrabeculectomy) to treat both diseases in one setting.1 Trabeculectomy, alone or in combination with other surgical procedures, is associated with a significant risk of complications. These include hypotony, shallowing of anterior chamber, malignant glaucoma, and endophthalmitis.2,3 A thick and anteriorly positioned lens has an important role in causing angle closure.4 –10 Lens extraction significantly widens the drainage angle11–14 and decreases intraocular pressure (IOP) in CACG eyes.11,15–23 Cataract extraction alone may therefore suffice as the primary treatment for CACG eyes with coexisting cataract, because it may treat both diseases at the same time. An earlier randomized controlled study compared the efficacy in IOP control of cataract extraction alone by © 2009 by the American Academy of Ophthalmology Published by Elsevier Inc.
phacoemulsification (phaco) versus combined phacotrabeculectomy with adjunctive mitomycin C chemotherapy in medically controlled CACG eyes with coexisting cataract.24 This article presents the results from a sister study that used the same study protocol but focused on another subgroup of patients with medically uncontrolled CACG eyes and cataract. “Medically uncontrolled” was defined as IOP greater than 21 mmHg despite maximally tolerated medications or requiring more than 3 topical drugs for IOP control.
Materials and Methods The authors obtained prior approval of the study protocol by the Ethics Committees of the Chinese University of Hong Kong, Hong Kong Eye Hospital, United Christian Hospital, and Prince of Wales Hospital. The research protocol adheres to the tenets of the Declaration of Helsinki. The study protocol was registered with the Centre for Clinical Trials of the Chinese University of Hong Kong, ISSN 0161-6420/09/$–see front matter doi:10.1016/j.ophtha.2008.12.054
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Ophthalmology Volume 116, Number 4, April 2009 which has been recognized by the International Committee of Medical Journal Editors for clinical trial registration (http:// 137.189.150.15/registry/publictriallist.php;date of access and registration: September 7, 2005). Informed consents were obtained from all patients before recruitment. Patients with medically uncontrolled CACG and cataract, and fulfilling the recruitment criteria in Table 1 (available at http:// aaojournal.org), were recruited. Only 1 eye from each patient could be recruited. If both eyes of 1 patient had coexisting CACG and cataract, the eye with the more mature cataract was included in the study. If both eyes had equally mature cataract, 1 eye was randomly selected for study using a random number table. Preoperative IOP (median of 3 Goldmann applanation readings taken on different days), number of IOP-lowering drugs, best corrected visual acuity (BCVA) by Snellen chart and converted to logarithm of the minimum angle of resolution (LogMAR) visual acuity, angle grading by indentation gonioscopy, vertical cup-todisk ratio (VCDR), and optic nerve head assessment by expert observer at the slit lamp using a 90D hand-held lens and with optic disc photography, and visual field (static automated white-onwhite threshold perimetry program 24- 2, SITA-standard, model 750, Humphrey Instruments, Dublin, CA) were documented for the study eye. The VCDR was taken to be the longest vertical cup diameter divided by the longest vertical disc diameter. The study eye was then randomized into 1 of 2 treatment groups using a random number table: phaco alone or combined phacotrabeculectomy with adjunctive mitomycin C chemotherapy. The surgical interventions in the 2 treatment groups are summarized in Table 2 (available at http://aaojournal.org). The procedures were performed under topical, retrobulbar, or peribulbar anesthesia, depending on patients’ or surgeons’ preferences, or clinical indications. Adjunctive mitomycin C was applied to the scleral surface before scleral incision (0.4 mg/ml). Standard application duration was 2 minutes, which was increased to 3 minutes if any of the following criteria were present: (a) extensive uveal manipulation anticipated, for example, significant posterior synechiae present; (b) young patient (age ⬍40 years); (c) previous failed trabeculectomy or phacotrabeculectomy in the fellow eye; and (d) prolonged use of topical IOP-lowering drugs, with conjunctival changes on slit-lamp examination. Postoperatively, study visits were scheduled at 1 day, 1 week, 1 month, 3 months, and then every 3 months for a minimum of 2 years, with documentation of IOP (median of 3 Goldmann applanation readings), number of IOP-lowering drugs required, BCVA, angle status by indentation gonioscopy, complications, additional interventions required to maintain filtration or handle complications, and VCDR. Observers were not masked from the surgery performed. Optic disc photography and visual field by Humphrey automated perimetry were repeated at annual intervals. Postoperatively, only eyes with an untreated IOP ⬎21 mmHg were resumed on IOP-lowering drugs to maintain an IOP of 21 mmHg or less. Glaucoma drugs were added in the following order: (1) beta-blockers, (2) prostaglandin analogues, (3) carbonic anhydrase inhibitors, (4) pilocarpine, (5) adrenergic agonists. Additional clinic visits and investigations were to be scheduled as and when required. All these were recorded in the datasheet.
served at 2 or more separate follow-up visits; (2) appearance of new splinter hemorrhage; (3) appearance of new or extension of old neuroretinal rim notching observed at 2 or more separate clinic visits; (4) appearance of new or extension of old nerve fiber layer defects observed at 2 or more separate clinic visits. Progression based on changes in Humphrey25 automated perimetry was as per published standard: defect deepened or enlarged if 2 or more points within or adjacent to an existing scotoma have worsened by at least 10 dB; all progression required confirmation on at least 1 subsequent field and clinical correlation with no other explanation for deterioration.
Outcome Measures
Statistical Methods
The primary outcome measures were IOP and the number of IOP-lowering drugs. Secondary outcome measures included BCVA, changes in optic nerve morphology and visual field, surgical complications, and need for additional surgical interventions. Progression based on changes in glaucomatous optic nerve head morphology was confirmed if 1 or more of the following criteria was fulfilled: (1) increase in VCDR of 0.1 or more ob-
All statistics were calculated using the Statistical Package for the Social Sciences 15.0 for Windows (SPSS Inc., Chicago, IL). Continuous data were expressed in mean ⫾ standard deviation and compared using the Student t test or Mann–Whitney U test as appropriate. Categoric data were expressed in percentages and compared using the chi-square test. A P value of ⬍0.05 was considered statistically significant.
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Indications for Additional Surgical Intervention in the Postoperative Period In both treatment groups, Yag capsulotomy was indicated if there was significant posterior capsular opacification causing a deterioration in BCVA. In the “phaco alone” group, secondary trabeculectomy was indicated if IOP increased to greater than 21 mmHg with 3 or more topical glaucoma drugs at more than 1 follow-up visit. In the combined phacotrabeculectomy group, suturing for conjunctival wound leak was performed if the leak did not stop after aqueous suppression and eye patching for 3 days. Laser suturelysis was indicated if IOP increased to greater than 21 mmHg from 1 week to 1 month after surgery without IOP-lowering drugs, whereas subconjunctival 5-fluorouracil injection was indicated if there was significant and persistent conjunctival congestion despite maximal topical steroid treatment in the postoperative period. Intervention for overdrainage was indicated if hypotony (IOP ⬍6 mmHg) persisted for more than 2 months in an eye with good visual prognosis or if complications (e.g., hypotony maculopathy) were detected. Interventions for overdrainage include conservative measures such as bleb compression and aqueous suppressants, and surgical procedures such as intra-bleb autologous blood injection, conjunctival suturing, or open revision of trabeculectomy, depending on the severity of hypotony and its complications.
Sample Size Calculation Sample size calculation was performed with the principal investigator’s own unpublished data (2001–2002) from a pilot study. The mean preoperative IOP (⫾ standard deviation) was 27.4 (⫾8.5) mmHg in the medically uncontrolled CACG eyes with cataract in the pilot study. The aim of the surgery was to achieve a “normal” untreated IOP, which was defined as 21 mmHg or less. Thus, the required reduction in IOP was 6.4 mmHg. On the basis of these data, and assuming an alpha of 0.05 and a power of 80%, to prove that the 2 interventions were equivalent in decreasing the IOP to the normal level, a minimum of 23 patients would be required in each arm.
Tham et al 䡠 Phaco versus Phacotrabeculectomy in Chronic Angle Closure Glaucoma Table 3. Patient Demographics of the Two Treatment Groups Combined Phacotrabeculectomy with Adjunctive Mitomycin C Group P Value
Phaco Group No. of eyes (No. of patients) Mean age ⫾ SD (yrs) Male : female ratio Left eye : right eye ratio
27 (27) 70.3⫾7.4 yrs (range, 52–83 yrs) 9 : 18 15 : 12
24 (24) 70.4⫾9.0 yrs (range, 55–91 yrs) 6 : 18 10 : 14
0.99* 0.51† 0.32†
SD ⫽ standard deviation. *Student t test. † Chi-square test.
Results Patient Demographics and Preoperative Clinical Status During the study recruitment period from March 2002 to October 2007, 51 medically uncontrolled CACG eyes with coexisting cataract of 51 patients were recruited. Of these 51 eyes, 27 were randomized into the “phaco alone” treatment group and 24 were randomized into the “combined phacotrabeculectomy with adjunctive mitomycin C chemotherapy” treatment group. Table 3 summarizes the patient demographics. There were more female than male patients in both treatment groups, but the difference between the groups did not reach statistical significance (P ⫽ 0.06). Table 4 summarizes the preoperative clinical status of the 2 treatment groups.
Surgical Procedures and Follow-up The surgical procedures were performed by 9 experienced glaucoma surgeons in 3 ophthalmic centers (Hong Kong Eye Hospital, United Christian Hospital, and Prince of Wales Hospital). In both treatment groups, all surgical procedures were performed under local anesthesia, including topical, retrobulbar, peribulbar, and subtenon anesthesias. Within the combined surgery group, 2 CACG eyes had mitomycin C application for 2 minutes, and 22 eyes had mitomycin C application for 3 minutes, in accordance with criteria in Table 2 (available at http://aaojournal.org).
Mean follow-up durations ⫾1 standard deviation were 33.4⫾ 10.5 months (range, 24.0 –53.5 months) in the “phaco alone” group and 37.6⫾10.3 months (range, 24.0 – 69.4 months) in the “combined phacotrabeculectomy with adjunctive mitomycin C chemotherapy” group (P ⫽ 0.2). In this article, the outcome measures up to the 24-month follow-up are reported.
Main Outcome Measures Figure 1 compares the IOP profiles of the 2 groups of patients. The IOP at various time points of follow-up for the 2 groups of patients is summarized in Table 5 (available at http://aaojournal.org). There were no statistically significant differences (P⬎0.05) in mean IOP between the 2 treatment groups preoperatively and postoperatively, except at 3 months (P ⫽ 0.01), 15 months (P ⫽ 0.02), and 18 months (P ⫽ 0.01). Within both treatment groups, the mean postoperative IOPs at all postoperative time points up to 24 months were statistically significantly lower (P⬍0.001) than the mean preoperative IOPs. No eyes in either treatment group had IOP of 6 mmHg or less at any postoperative time points. Table 6 (available at http://aaojournal.org) summarizes the mean number of topical glaucoma drugs at various time points of follow-up for the 2 groups of patients. Figure 2 compares the mean number of topical glaucoma drugs in the 2 groups of patients. There was no statistically significant difference (P ⫽ 0.45) in the mean preoperative number of glaucoma drugs between the 2 treatment groups. The mean numbers of topical glaucoma drugs required in the “combined phacotrabeculectomy with adjunctive
Table 4. Preoperative Clinical Status of the Two Treatment Groups Phaco Group
Combined Phacotrabeculectomy with Adjunctive Mitomycin C Group
Mean preoperative IOP ⫾ SD (mmHg) 24.4⫾6.1 mmHg (range, 14.0–38.0 mmHg) 23.8⫾4.3 mmHg (range, 15.0–32.0 mmHg) Mean No. of preoperative IOP-lowering 3.3⫾1.1 (range, 2–5) 3.1⫾0.9 (range, 2–5) drugs ⫾ SD Mean preoperative BCVA ⫾ SD (LogMar) 0.8⫾0.7 (range, 0.4–3.0) 0.7⫾0.4 (range, 0.4–1.6) Extent of synechial angle closure ⫾ SD 275.0⫾54.1 degrees (range, 180–360 degrees) 256.9⫾72.0 degrees (range, 180–360 degrees) (degrees) Mean VCDR ⫾ SD 0.8⫾0.2 (range, 0.3–0.9) 0.7⫾0.2 (range, 0.4–1.0) Automated perimetry: Mean MD ⫾ SD (db) ⫺17.5⫾11.4 db (range, ⫺2.1 to ⫺31.3 db) ⫺16.6⫾11.2 db (range, ⫺2.2 to ⫺32.1 db) Automated perimetry: Mean PSD ⫾ SD (db) 5.1⫾3.4 db (range, 1.7–14.7 db) 4.8⫾3.3 db (range 1.5–12.4 db) Eyes with history of acute angle closure 7/27 6/24 attack
P Value 0.72* 0.45* 0.56* 0.31* 0.34* 0.79* 0.74* 0.94†
BCVA ⫽ best corrected visual acuity; db ⫽ decibel; IOP ⫽ intraocular pressure; LogMAR ⫽ logarithm of the minimum angle of resolution; MD ⫽ mean deviation; PSD ⫽ pattern standard deviation; SD ⫽ standard deviation; VCDR ⫽ vertical cup-to-disk ratio. *Student t test. † Chi-square test.
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Figure 1. Intraocular pressure profiles of phaco and phacotrabeculectomy groups.
mitomycin C chemotherapy” treatment group were statistically significantly lower (P⬍0.001) than the mean numbers of topical glaucoma drugs in the “phaco alone” group at all postoperative time points. None of the study patients required systemic IOPlowering drugs to control IOP either preoperatively or postoperatively. During the 24-month postoperative follow-up period, the mean postoperative number of topical glaucoma drugs in the “combined phaco-trabeculectomy with adjunctive mitomycin C chemotherapy” treatment group were on average 1.25 lower than the mean postoperative number of topical glaucoma drugs in the “phaco alone” group (P⬍0.001). At 24 months, 7 of 27 (25.9%) “phaco alone” eyes did not require any glaucoma drugs, whereas 17 of 24 (70.8%) combined phacotrabeculectomy eyes did not require any glaucoma drugs. In both treatment groups, the mean postoperative number of topical glaucoma drugs at all postoperative time points was statistically significantly lower (P⬍0.001) than the mean preoperative number of topical glaucoma drugs. Table 7 summarizes the proportion of CACG cases with controlled IOP after the 2 treatments. By applying the same definition of “medically controlled” as applied in our previous study,24 both treatments achieved more than 90% of IOP control at both 12 and 24 months after surgery, and there was no statistically significant difference between the 2 treatments at both time points.
In the “phaco alone” group, 1 eye had worse LogMAR BCVA at 2 years compared with before surgery. This eye had progression of age-related macular degeneration with extension of macular scarring and did not have any surgical complications. In the combined surgery group, 4 eyes had worse LogMAR BCVA at 2 years compared with before surgery. All 4 eyes had very advanced glaucomatous optic neuropathy and visual field loss before surgery. Two eyes had immediate deterioration in visual acuity after surgery (“wipe-out” phenomenon). These 2 eyes did not have any intraoperative surgical complications. The other 2 eyes had poor IOP control and gradual progression of glaucomatous optic neuropathy during the 2 years of follow-up. One of these 2 eyes had needling revision of the trabeculectomy site with adjunctive 5-fluorouracil chemotherapy performed twice, whereas the other eye had repeated subconjunctival injections of 5-fluorouracil (5 mg) in the early postoperative period and needling revision with adjunctive 5-fluorouracil chemotherapy performed once. There were no statistically significant differences in mean VCDR between the 2 groups preoperatively and at the 12- and 24-month follow-ups. Within the “phaco alone” group, there were no statistically significant changes in mean VCDR at both the 12and 24-month follow-ups compared with the preoperative status. Within the combined surgery group, there were statistically significant increases in VCDR at both the 12-month (P ⫽ 0.001) and 24-month (P⬍0.001) follow-ups, compared with the preoperative status. On the basis of our definition of progression of glaucomatous optic neuropathy outlined above, none of the 27 CACG eyes (0%) in the “phaco alone” group demonstrated progression during the 2-year follow-up period, whereas 4 of the 24 CACG eyes (16.7%) in the “combined phacotrabeculectomy with adjunctive mitomycin C chemotherapy” treatment group demonstrated progression during the 2-year follow-up period (P ⫽ 0.03, 2 test). There were no statistically significant differences in mean pattern standard deviation on Humphrey automated perimetry between the 2 groups preoperatively and at the 12- and 24-month follow-ups. Within each treatment group, there were no statisti-
Secondary Outcome Measures Table 8 summarizes the mean LogMAR BCVA of the 2 treatment groups at various time points. There were no statistically significant differences in mean LogMAR BCVA between the 2 groups preoperatively and at the 12- and 24-month follow-ups. Within the “phaco alone” group, there was statistically significant (P ⫽ 0.001) improvement in mean LogMAR BCVA at both the 12- and 24month follow-ups compared with the preoperative status. Within the “combined phacotrabeculectomy with adjunctive mitomycin C chemotherapy” treatment group, the mean LogMAR BCVA at the 12- and 24-month follow-ups was better than the preoperative mean LogMAR BCVA, but the differences did not reach statistical significance (P ⫽ 0.24 for 12 months, and P ⫽ 0.68 for 24 months).
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Figure 2. Profiles of requirements for topical glaucoma drugs in the 2 treatment groups.
Tham et al 䡠 Phaco versus Phacotrabeculectomy in Chronic Angle Closure Glaucoma Table 7. Proportion of Chronic Angle Closure Glaucoma Cases with Controlled Intraocular Pressure after the Two Treatments No. of CACG Eyes with IOP Controlled Phaco Group Combined Phacotrabeculectomy with by Medications* (Percentages) (n ⴝ 27) Adjunctive Mitomycin C Group (n ⴝ 24) P Value† Preoperative 12 mos after surgery 24 mos after surgery
0 (0%) 25 (92.6%) 25 (92.6%)
0 (0%) 24 (100%) 22 (91.7%)
0.17 0.90
CACG ⫽ chronic angle closure glaucoma; IOP ⫽ intraocular pressure. *Based on the definitions in this study. † Chi-square test.
cally significant changes in mean pattern standard deviation at both the 12- and 24-month follow-ups compared with the preoperative status. On the basis of our definition of progression of glaucomatous visual field outlined previously, 11 of the 27 CACG eyes (40.7%) in the “phaco alone” group demonstrated progression during the 2-year follow-up period, whereas 9 of the 24 CACG eyes (37.5%) in the “combined phacotrabeculectomy with adjunctive mitomycin C chemotherapy” treatment group demonstrated progression during the 2-year follow-up period (P ⫽ 0.81, 2 test). There was no statistically significant difference between the 2 treatment groups in the number of intraoperative complications (P ⫽ 0.74). The “combined phacotrabeculectomy with adjunctive mitomycin C chemotherapy” treatment group had significantly more postoperative complications (8 complications) than the “phaco alone” group (0 complications) (P ⫽ 0.001). There were no statistically significant differences between the 2 treatment groups in the number of additional surgical interventions required to control IOP or to manage complications (P ⫽ 0.21 and 0.13, respectively). Four eyes (14.8%) in the “phaco alone” group subsequently required trabeculectomy to control IOP during the 24month follow-up. All 4 cases did not have surgical complications and had IOP controlled up to 24 months after the initial phacoemulsification. Details of these complications, their management and outcomes, and the additional surgical interventions will be presented in a subsequent publication.
Discussion Two sister randomized controlled clinic trials were undertaken in Hong Kong to compare the efficacy in IOP control of cataract extraction alone by phacoemulsification versus combined phacotrabeculectomy with adjunctive mitomycin C chemotherapy in CACG eyes with coexisting cataract.
The other study24 focused on the subgroup of CACG eyes with medically controlled IOP before surgery, whereas this study focused on those CACG eyes with medically uncontrolled IOP before surgery. Table 9 (available at http:// aaojournal.org) summarizes the key difference in recruitment criteria and the clinical outcomes of the 2 randomized controlled trials. From both trials, it is clear that phacoemulsification alone is effective in improving IOP control, both in terms of decreasing IOP and reducing the requirement for glaucoma drugs, in CACG eyes with cataract, whether the preoperative IOP is medically controlled or not. Combined phacotrabeculectomy resulted in lower mean IOP than phaco alone at all time points up to 24 months after surgery, whether the preoperative IOP was controlled or not. However, this difference reached statistical significance in only a minority of time points. Combined phacotrabeculectomy resulted in the requirement of significantly fewer glaucoma drugs than phaco alone at all time points up to 24 months after surgery, whether the preoperative IOP was controlled (average 0.80 fewer drugs over 24 months) or uncontrolled (average 1.25 fewer drugs over 24 months). When the definition of “medically controlled” from our previous publication24 was used, there was no statistically significant difference between the 2 treatments in the proportion of cases that became “medically controlled” at both 12 and 24 months after surgery (Table 7). On the basis of these findings, combined phacotrabeculectomy seemed to be more effective than phaco alone in controlling IOP in CACG eyes with cataract, but the difference appeared marginal and was mainly in a lower requirement for glaucoma drugs. Using an average of 1 less glau-
Table 8. Mean Logarithm of the Minimum Angle of Resolution Best Corrected Visual Acuity of the Two Treatment Groups at Various Time Points LogMAR BCVA
Phaco Group
Mean preoperative ⫾ SD 0.8⫾0.7 (range, 0.4–3.0) Mean postoperative at 12 mos ⫾ SD 0.6⫾0.7 (range, 0.0–3.0) Mean postoperative at 24 mos ⫾ SD 0.6⫾0.7 (range, 0.0–3.0)
Combined Phacotrabeculectomy with Adjunctive Mitomycin C Group P Value* 0.7⫾0.4 (range, 0.4–1.6) 0.5⫾0.6 (range, 0.1–3.0) 0.6⫾0.8 (range, 0.2–3.0)
0.56 0.84 0.77
BCVA ⫽ best corrected visual acuity; LogMAR ⫽ logarithm of the minimum angle of resolution; SD ⫽ standard deviation. *Student t test.
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Ophthalmology Volume 116, Number 4, April 2009 coma drug during a 24-month period may mean less adverse drug effects and convenience for the patients, improved compliance with the remaining drugs, and lower cost to patients or society; however, there was a price to pay for the mean difference of approximately 1 glaucoma drug between the 2 treatments, and this included significantly more postoperative complications in the combined phacotrabeculectomy group in both studies and significantly more cases with progression of glaucomatous optic neuropathy in the combined phacotrabeculectomy group in the CACG eyes with uncontrolled preoperative IOP (current study). These differences were, however, not reflected in the BCVA or the performance (pattern standard deviation) in automated perimetry. A detailed analysis of the functional outcomes and the impact on the patients’ quality of life will be presented in a subsequent publication. There are inherent weaknesses in our study design. Although the phacoemulsification procedure was well standardized, there were bound to be small individual variations in surgical techniques in trabeculectomy between the surgeons. Furthermore, this study was powered to study the differences in IOP control between the 2 treatment groups. This study may not have sufficient power (sample size) and follow-up duration to look at other parameters, such as complications and glaucomatous progression. The results from these 2 studies are not applicable to those CACG cases with no coexisting cataract. To respect patients’ and surgeons’ preference, we were not able to standardize the type of anesthesia, which may have an influence on the clinical outcome. For example, subtenon or peribulbar anesthesia may be more likely to influence bleb formation than general anesthesia. Retrobulbar anesthesia may affect the optic nerve and the visual field in the final stages of glaucoma. On the basis of the data from these 2 studies, phacoemulsification alone is a viable surgical alternative to combined phacotrabeculectomy in CACG eyes with coexisting cataract, whether the preoperative IOP is medically controlled or not. The additional postoperative complications in the combined surgery group may not be justified by the small additional lowering in the requirement of glaucoma drugs. Although a small proportion (14.8% in the current study with uncontrolled preoperative IOP and 2.9% in the previous publication24 with controlled preoperative IOP) of phacotreated CACG eyes require a subsequent trabeculectomy for IOP control, there is no available evidence to suggest that these eyes will do worse than eyes receiving combined surgery, in terms of long-term visual outcomes, IOP control, or complications.
References 1. Lai JS, Tham CC, Lam DS. Incisional surgery for angle closure glaucoma. Semin Ophthalmol 2002;17:92–9. 2. Bellucci R, Perfetti S, Babighian S, et al. Filtration and complications after trabeculectomy and after phaco-trabeculectomy. Acta Ophthalmol Scand Suppl 1997;(224):44 –5. 3. Tham CC, Lai JS, Poon AS, et al. Results of trabeculectomy with adjunctive intraoperative mitomycin C in Chinese patients with glaucoma. Ophthalmic Surg Lasers Imaging 2006; 37:33– 41.
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4. Foster PJ. The epidemiology of primary angle closure and associated glaucomatous optic neuropathy. Semin Ophthalmol 2002;17:50 – 8. 5. 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: 633– 42. 6. Lowe RF. Causes of shallow anterior chamber in primary angle-closure glaucoma: ultrasonic biometry of normal and angle-closure glaucoma eyes. Am J Ophthalmol 1969;67: 87–93. 7. Lowe RF. Aetiology of the anatomical basis for primary angle-closure glaucoma: biometrical comparisons between normal eyes and eyes with primary angle-closure glaucoma. Br J Ophthalmol 1970;54:161–9. 8. Markowitz SN, Morin JD. Angle-closure glaucoma: relation between lens thickness, anterior chamber depth and age. Can J Ophthalmol 1984;19:300 –2. 9. Tornquist R. Chamber depth in primary acute glaucoma. Br J Ophthalmol 1956;40:421–9. 10. Wojciechowski R, Congdon N, Anninger W, Teo Broman A. Age, gender, biometry, refractive error, and the anterior chamber angle among Alaskan Eskimos. Ophthalmology 2003;110: 365–75. 11. Di Staso S, Sabetti L, Taverniti L, et al. Phacoemulsification and intraocular lens implant in eyes with primary angleclosure glaucoma: our experience. Acta Ophthalmol Scand Suppl 2002;236:17– 8. 12. Hayashi K, Hayashi H, Nakao F, Hayashi F. Changes in anterior chamber angle width and depth after intraocular lens implantation in eyes with glaucoma. Ophthalmology 2000; 107:698 –703. 13. Tran HV, Liebmann JM, Ritch R. Iridociliary apposition in plateau iris syndrome persists after cataract extraction. Am J Ophthalmol 2003;135:40 –3. 14. Yang CH, Hung PT. Intraocular lens position and anterior chamber angle changes after cataract extraction in eyes with primary angle-closure glaucoma. J Cataract Refract Surg 1997;23:1109 –13. 15. Acton J, Salmon JF, Scholtz R. Extracapsular cataract extraction with posterior chamber lens implantation in primary angle-closure glaucoma. J Cataract Refract Surg 1997;23:930 – 4. 16. Greve EL. Primary angle closure glaucoma: extracapsular cataract extraction or filtering procedure? Int Ophthalmol 1988;12:157– 62. 17. Gunning FP, Greve EL. Uncontrolled primary angle closure glaucoma: results of early intercapsular cataract extraction and posterior chamber lens implantation. Int Ophthalmol 1991;15: 237– 47. 18. Gunning FP, Greve EL. Lens extraction for uncontrolled angleclosure glaucoma: long-term follow-up. J Cataract Refract Surg 1998;24:1347–56. 19. Wishart PK, Atkinson PL. Extracapsular cataract extraction and posterior chamber lens implantation in patients with primary chronic angle-closure glaucoma: effect on intraocular pressure control. Eye 1989;3:706 –12. 20. Ge J, Guo Y, Liu Y, et al. New management of angle-closure glaucoma by phacoemulsification with foldable posterior chamber intraocular lens implantation. Yan Ke Xue Bao 2000; 16:22– 8. 21. Hayashi K, Hayashi H, Nakao F, Hayashi F. Effect of cataract surgery on intraocular pressure control in glaucoma patients. J Cataract Refract Surg 2001;27:1779 – 86. 22. Kubota T, Toguri I, Onizuka N, Matsuura T. Phacoemulsification and intraocular lens implantation for angle closure
Tham et al 䡠 Phaco versus Phacotrabeculectomy in Chronic Angle Closure Glaucoma glaucoma after the relief of pupillary block. Ophthalmologica 2003;217:325– 8. 23. Lai JS, Tham CC, Chan JC. 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: 47–52.
24. Tham CC, Kwong YY, Leung DY, et al. Phacoemulsification versus combined phacotrabeculectomy in medically controlled chronic angle closure glaucoma with cataract. Ophthalmology 2008;115:2167–73. 25. Anderson DR, Chauhan B, Johnson C, et al. Criteria for progression of glaucoma in clinical management and in outcome studies. Am J Ophthalmol 2000;130:827–9.
Footnotes and Financial Disclosures Originally received: August 12, 2008. Final revision: December 12, 2008. Accepted: December 19, 2008. Available online: February 25, 2009.
Supported by a Direct Grant for Research from the Chinese University of Hong Kong 2004 –2005. The funding organization had no role in the design or conduct of this research. Manuscript no. 2008-965.
1
Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China. 2
Hong Kong Eye Hospital, Kowloon, Hong Kong SAR, People’s Republic of China. 3
Prince of Wales Hospital, Shatin, N.T., Hong Kong SAR, People’s Republic of China. 4
Department of Ophthalmology, United Christian Hospital, Kowloon, Hong Kong SAR, People’s Republic of China.
Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Correspondence: Clement C. Y. Tham, FRCS, Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong Eye Hospital, 147K Argyle Street, Kowloon, Hong Kong. E-mail: clemtham@hkstar. com.
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Ophthalmology Volume 116, Number 4, April 2009 Table 1. Recruitment Criteria Diagnostic criteria for medically controlled CACG:
Diagnostic criteria for cataract: Inclusion criteria: Exclusion criteria:
At least 180 degrees of angle closure obliterating pigmented part of trabecular meshwork, whether synechial or appositional, segmented or continuous, in the presence of a patent peripheral iridotomy; requiring IOP-lowering medications, or IOP ⬎21 mmHg without IOP-lowering medications; visual field loss compatible with glaucoma* and/or glaucomatous optic disc changes Definition of “medically uncontrolled”: IOP ⬎21 mmHg despite maximally tolerated medications or requiring ⬎3 topical drugs for IOP control (combination drugs counted as 2 drugs) Presence of nucleus sclerosis, cortical cataract, or subcapsular cataract; visual acuity of 20/50 or worse, and affecting activities of daily living Eyes with CACG and coexisting cataract as defined above Patient able and willing to give informed consent to phacoemulsification or combined phacotrabeculectomy, before randomization Single functional eye; patients refusing either cataract extraction or trabeculectomy; previous intraocular surgery, with the exception of laser peripheral iridotomy and argon laser peripheral iridoplasty
CACG ⫽ chronic angle closure glaucoma; IOP ⫽ intraocular pressure. *Minimal criteria for glaucomatous visual field defect as per published standard:25 glaucoma hemifield test outside normal limits, pattern standard deviation with a P value of ⬍5%, or a cluster of ⱖ3 points in the pattern deviation plot in a single hemifield (superior or inferior) with P value of ⬍5%, one of which must have a P value of ⬍1%. Any one of the preceding criteria, if repeatable, was considered sufficient evidence of a glaucomatous visual field defect.
Table 2. Interventions in the Two Treatment Groups after Randomization Phacoemulsification Group
Combined Phacotrabeculectomy Group
Any topical pilocarpine was stopped for 1 wk before phaco (other eye medications continued up to and beyond phaco). Corneal incisions were used to preserve conjunctiva for future filtration surgery. Posterior synechialysis, pupil stretching by Kuglen hooks, and the use of iris hooks to maintain an enlarged pupil were used where indicated. Foldable and injectable intraocular lenses were implanted into the capsular bag whenever possible. A complete evacuation of viscoelastic agent was attempted in every case at the end of surgery. Topical Prednisol 1% and topical chloramphenicol were given postoperatively. Frequency and duration were dictated by clinical needs. Postoperatively, 1 stat dose of 250 mg oral acetazolamide was given as prophylaxis against IOP spike. Additional oral acetazolamide could be given to treat IOP spike as indicated. Postoperatively, any glaucoma eyedrops were tailed down if the mean IOPs at 2 consecutive visits were ⱕ21 mmHg. The order of stopping drugs was the reverse of the order of resuming drugs, i.e., adrenergic agonists first, followed by pilocarpine, carbonic anhydrase inhibitors, prostaglandin analogues, and beta-blockers.
Any topical pilocarpine was stopped for 1 wk before phacotrabeculectomy (other eye medications continued up to day of phacotrabeculectomy). Either 1- or 2-site phacotrabeculectomy could be performed, depending on surgeon’s preference. Adjunctive MMC was applied to the scleral surface before scleral incision (0.4 mg/ml). Standard application duration was 2 min, which was increased to 3 min if any of the following criteria were present: Extensive uveal manipulation anticipated, e.g., significant posterior synechiae present Young patient (age ⬍40 yrs) Previous failed trabeculectomy or phacotrabeculectomy in fellow eye Prolonged use of topical IOP-lowering drugs, with conjunctival changes on slit-lamp examination Posterior synechialysis, pupil stretching by Kuglen hooks, and the use of iris hooks to maintain an enlarged pupil were used where indicated. Foldable and injectable intraocular lenses were implanted into the capsular bag whenever possible. A complete evacuation of viscoelastic agent was attempted in every case at the end of surgery. Topical Prednisol 1% and topical chloramphenicol were given postoperatively. Frequency and duration were dictated by clinical needs. Postoperatively, laser suturelysis was performed if there was no bleb and IOP increased ⬎21 mmHg.
IOP ⫽ intraocular pressure; MMC ⫽ mitomycin C.
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Tham et al 䡠 Phaco versus Phacotrabeculectomy in Chronic Angle Closure Glaucoma Table 5. Intraocular Pressure at Various Time Points of Follow-up for the Two Groups of Study Patients Phaco Group Mean preoperative IOP ⫾ SD (mmHg) Mean 1-mo postoperative IOP ⫾ SD (mmHg) Mean 3-mo postoperative IOP ⫾ SD (mmHg) Mean 6-mo postoperative IOP ⫾ SD (mmHg) Mean 9-mo postoperative IOP ⫾ SD (mmHg) Mean 12-mo postoperative IOP ⫾ SD (mmHg) Mean 15-mo postoperative IOP ⫾ SD (mmHg) Mean 18-mo postoperative IOP ⫾ SD (mmHg) Mean 21-mo postoperative IOP ⫾ SD (mmHg) Mean 24-mo postoperative IOP ⫾ SD (mmHg)
Combined Phacotrabeculectomy with Difference in Mean IOP Adjunctive Mitomycin C Group between 2 Groups
P Value*
24.4⫾6.1 (range, 14.0–38.0) 15.7⫾3.9 (range, 8.0–22.0)
23.8⫾4.3 (range, 15.0–32.0) 13.7⫾3.4 (range, 9.0–21.0)
0.6 mmHg 2.0 mmHg
0.72 0.05
17.0⫾3.3 (range, 12.0–25.0)
14.0⫾4.2 (range, 8.0–24.0)
3.0 mmHg
0.01
16.3⫾3.5 (range, 10.0–25.0)
14.8⫾4.7 (range, 9.0–26.0)
1.5 mmHg
0.19
15.9⫾3.3 (range, 10.0–24.0)
14.6⫾3.3 (range, 10.0–20.0)
1.2 mmHg
0.20
15.5⫾3.2 (range, 10.0–22.0)
14.0⫾4.4 (range 7.0–22.0)
1.5 mmHg
0.16
15.4⫾3.2 (range, 10.0–22.0)
13.2⫾3.2 (range, 10.0–21.0)
2.2 mmHg
0.02
15.9⫾3.0 (range, 11.0–22.0)
13.6⫾3.4 (range 10.0–21.0)
2.3 mmHg
0.01
16.1⫾3.6 (range, 11.0–27.0)
14.1⫾4.2 (range 9.0–25.0)
2.0 mmHg
0.07
16.1⫾4.1 (range, 9.0–27.0)
14.1⫾3.7 (range 9.0–22.0)
2.0 mmHg
0.08
IOP ⫽ intraocular pressure; SD ⫽ standard deviation. *Student t test.
Table 6. Number of Topical Glaucoma Drugs Required at Various Time Points of Follow-up for the Two Groups of Study Patients
Mean preoperative No. of glaucoma drugs ⫾ SD Mean 3-mo postoperative No. of glaucoma drugs ⫾ SD Mean 6-mo postoperative No. of glaucoma drugs ⫾ SD Mean 9-mo postoperative No. of glaucoma drugs ⫾ SD Mean 12-mo postoperative No. of glaucoma drugs ⫾ SD Mean 15-mo postoperative No. of glaucoma drugs ⫾ SD Mean 18-mo postoperative No. of glaucoma drugs ⫾ SD Mean 21-mo postoperative No. of glaucoma drugs ⫾ SD Mean 24-mo postoperative No. of glaucoma drugs ⫾ SD
Phaco Group
Combined Phacotrabeculectomy with Adjunctive Mitomycin C Group
Difference in Mean No. of Topical Glaucoma Drugs between the 2 Groups
P Value*
3.3⫾1.1 (range, 2–5)
3.1⫾0.9 (range, 2–5)
0.2
0.45
1.5⫾1.2 (range, 0–3)
0.3⫾0.8 (range, 0–3)
1.2
⬍0.001
1.5⫾1.3 (range, 0–4)
0.3⫾0.7 (range, 0–3)
1.2
⬍0.001
1.5⫾1.4 (range, 0–4)
0.4⫾0.9 (range, 0–3)
1.1
⬍0.001
1.5⫾1.4 (range, 0–4)
0.3⫾0.6 (range, 0–2)
1.2
⬍0.001
1.6⫾1.4 (range, 0–4)
0.3⫾0.5 (range, 0–2)
1.3
⬍0.001
1.6⫾1.4 (range, 0–4)
0.3⫾0.6 (range, 0–2)
1.3
⬍0.001
1.7⫾1.4 (range, 0–4)
0.3⫾0.8 (range, 0–3)
1.4
⬍0.001
1.7⫾1.3 (range, 0–4)
0.5⫾1.0 (range, 0–4)
1.2
⬍0.001
SD ⫽ standard deviation. *Student t test.
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Ophthalmology Volume 116, Number 4, April 2009 Table 9. Summary of Recruitment Criteria and Clinical Outcomes of Two Randomized Controlled Trials on Chronic Angle Closure Glaucoma with Coexisting Cataract Previous RCT on Medically Controlled CACG with Cataract24
Current RCT on Medically Uncontrolled CACG with Cataract
Key difference in recruitment criteria
“Medically controlled” defined as IOP ⱕ21 mmHg, with ⱕ3 topical drugs
IOP
No significant differences (P⬎0.05) in mean IOP between the 2 treatment groups preoperatively and postoperatively, except at 1 mo (P ⫽ 0.001) and 3 mos (P ⫽ 0.008). The “combined phacotrabeculectomy” group required statistically significantly fewer drugs (P⬍0.001) than the “phaco alone” group at all postoperative time points. Over the 24-mo follow-up period, the mean postoperative No. of topical glaucoma drugs in the “combined phacotrabeculectomy” group were on average 0.80 lower than in the “phaco alone” group (P⬍0.001) No statistically significant difference between 2 treatment groups No statistically significant difference between 2 treatment groups Significantly more complications in the combined phacotrabeculectomy group No statistically significant difference between 2 treatment groups No statistically significant difference between 2 treatment groups No statistically significant difference between 2 treatment groups
“Medically uncontrolled” defined as IOP ⬎21 mmHg despite maximally tolerated medications or requiring ⬎3 topical drugs for IOP control No significant differences (P⬎0.05) in mean IOP between the 2 treatment groups preoperatively and postoperatively, except at 3 mos (P ⫽ 0.01), 15 mos (P ⫽ 0.02), and 18 mos (P ⫽ 0.01). The “combined phacotrabeculectomy” group required statistically significantly fewer drugs (P⬍0.001) than the “phaco alone” group at all postoperative time points. Over the 24-mo follow-up period, the mean postoperative No. of topical glaucoma drugs in the “combined phacotrabeculectomy” group were on average 1.25 lower than in the “phaco alone” group (P⬍0.001)
Requirement for topical glaucoma drugs
Mean LogMAR BCVA before surgery and at 12 and 24 mos after surgery Intraoperative complications Postoperative complications Additional surgical interventions Progression of GON Progression of GVFL
No statistically significant difference between 2 treatment groups No statistically significant difference between 2 treatment groups Significantly more complications in the combined phacotrabeculectomy group No statistically significant difference between 2 treatment groups Significantly more cases in the combined phacotrabeculectomy group No statistically significant difference between 2 treatment groups
BCVA ⫽ best corrected visual acuity; CACG ⫽ chronic angle closure glaucoma; GON ⫽ glaucomatous optic neuropathy; GVFL ⫽ glaucomatous visual field loss; IOP ⫽ intraocular pressure; LogMAR ⫽ logarithm of the minimum angle of resolution; RCT ⫽ randomized controlled trial.
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