【摘要】 目的：评价并比较一切口和二切口超声乳化白内障吸除术联合小梁切除术治疗白内障合并青光眼的疗效和耐受性。方法：按照Cochrane协作网方法全面检索符合纳入标准的比较一切口和二切口超声乳化白内障吸除术联合小梁切除术的临床对照研究，将其进行荟萃分析。临床疗效的评估包括：眼压下降百分比采用标准化均差(SMD)，术后最佳矫正视力≥0.5的患者百分比采用比值比(OR)，手术成功率采用相对危险度(RR)。临床耐受性的评估采用RR。所有结果均以95%可信区间表示。数据分析采用Stata 10.1。结果：降低眼压的临床疗效二切口术式明显优于一切口术式，差异具有统计学意义(SMD，0.19;95% CI，0.33到 0.04;P=0.01);术后最佳矫正视力≥ 0.5的患者百分比二切口术式大于一切口术式，但差异不具有统计学意义(OR，0.65;95% CI，0.30到1.39;P=0.26);术后不加用抗青光眼药物达到靶眼压的患者百分比二切口术式大于一切口术式，但差异不具有统计学意义(RR, 0.94; 95% CI, 0.84到1.04; P=0.22);两种术式在术后并发症方面差别无统计学意义。结论：二切口超声乳化白内障吸除术联合小梁切除术临床疗效优于一切口术式。两种术式的术后并发症没有明显差异。
With the increasing elderly population and concurrent longevity in life expectancy, there is an increase in the incidence of coexisting visually significant cataract and glaucoma. One of the challenges in the management of surgical procedure is difficulty in solving these two problems simultaneously. Phacoemulsification alone may be beneficial in some cases, which results in better intraocular pressure (IOP) than planned extracapsular cataract extraction procedures, and performing the glaucoma filtering surgery first and the cataract surgery later may best serve others. However, there is a widespread shift towards the use of combined phacotrabeculectomy as the surgical treatment of choice for coexisting cataract and glaucoma in recent years.
Phacotrabeculectomy can be performed either using onesite or twosite incisions. The earliest clinical studies of phacotrabeculectomy which is known as a onesite procedure reported surgical results using the same the scleral tunnel incision for both the phacoemulsification and trabeculectomy parts of the surgery. The introduction of the temporal incision for phacoemulsification has allowed surgeons to perform twosite procedure, with a prelimbal filtering incision for the trabeculectomy and a separate clear cornea incision for phacoemulsification. Comparing of the two surgical procedures, previous studies generally had small sample sizes and showed conflicting results, which greatly hindered researchers drawing correct conclusions.
A metaanalysis of controlled clinical trials (prospective or retrospective) was conducted to assess the efficacy and tolerability of two surgical procedures for the management of coexisting cataract and glaucoma: onesite and twosite phacotrabeculectomy. This metaanalysis was designed to help resolve ambiguity regarding optimal management of coexisting cataract and glaucoma by pooling the outcome of available studies. Our analysis controlled for differences in study sizes and patient characteristics. However, we recognize the limitations introduced by differences in study protocols, publication bias, and the quality of studies.
MATERIALS AND METHODS
Search Strategy A computerized literature search was conducted in the PubMed, EMBASE, Scientific Citation Index and Cochrane Controlled Trials Register for relevant articles published up to May 2009. And extensive search for meeting archives, including the annual meeting abstracts of American Association of Ophthalmology (AAO) and Association for Research in Vision and Ophthalmology (ARVO) was also carried out up to May 2009. These databases were searched systematically using the following key words: phacotrabeculectomy, phacoemulsification and trabeculectomy, combined phacoemulsification and trabeculectomy, combined phaco/trabeculectomy, combined cataract and glaucoma surgery, combined cataractglaucoma surgery,onesite phacotrabeculectomy, twosite phacotrabeculectomy. The search strategy used both keywords and Medical Subject Headings (MeSH) terms. There were no limits placed on the language of publication. All potentially relevant nonEnglish publications were to be translated into English for further assessment. Literature reference proceedings were searched manually at the same time. The title and abstract of all potentially relevant articles were screened to determine their relevance. Then, full articles were scrutinized if the title and abstract were ambiguous. References identified from bibliographies of pertinent articles or books also were retrieved. References of included publications were reviewed until no further relevant studies were found.
Inclusion and exclusion criteria Only controlled clinical trials directly comparing between onesite and twosite phacotrabeculectomy in patients with coexisting cataract and glaucoma were included, antimetabolites could be used intraoperatively. Studies needed to have measured efficacy, tolerability or both in humans. Outcome variables included at least one of the following primary outcome variables: intraocular pressure reduction (IOPR), the percentage having a bestcorrected visual acuity (BCVA) of 0.5 or better after surgery, complete success rates and adverse events, or relevant data. Abstracts from conferences and full texts without raw data available for retrieval, duplicate publications, letter and review were excluded.
Studies selection The assessment of the titles and abstracts for eligibility was conducted by two independent reviewers (Liu HN and Nie QZ). Articles of potential interest were retrieved and their inclusion was reassessed. Disagreement at each step was resolved with discussion between the two reviewers. We obtained the full article of any study that seemed to fit the inclusion criteria.
Data extraction Two reviewers (Liu HN and Nie QZ) performed the data extraction that were included independently. Any differences were resolved by discussion to reach consensus among the investigators. A customized form was used to record authors of study, publication year, location, design, followup time, sample size, patient characteristics, interventions, baseline and endpoint values, and adverse events.
Outcome measures For efficacy, we used the percentage intraocular pressure reduction (IOPR%) in preoperative to postoperative IOP. Secondary efficacy measure was the percentage having a postoperative BCVA of 0.5 or better and complete success rate, which was defined as the proportion of patients achieved the target IOP without antiglaucoma medication at the end point. We assessed tolerability to phacotrabeculectomy by considering the proportions of patients with adverse events, including hyphema, choroidal detachment, bleb leak, hypotony, posterior capsule opacification and shallow anterior chamber.
Statistical analysis Extracted data were pooled for summary estimates using Stata 10.1 for Windows (StataCorp LP, College Station, TX, USA). Continuous outcomes were expressed as standardised mean difference (SMD), with values <0 favouring twosite phacotrabeculectomy,and dichotomous outcomes as odds ratio (OR) or relative risk (RR). Both outcomes were reported with 95% confidence interval (CI). P<0.05 was considered statistically significant on the test for overall effect. Intertrial statistical heterogeneity was explored using the DerSimonian and Laird Q test, with calculated I2 indicating the percentage of the total variability in effect estimates among trials that is due to heterogeneity rather than chance. If heterogeneity tests were nonsignificant, fixed effects models were used, as they provide narrower 95% CIs than the equivalent random effects models, which are more appropriate where significant heterogeneity is detected. The Begg and Egger tests were used to assess for publication bias.
For studies that only reported absolute values for IOP at baseline and end point, the IOPR, standard deviation (SD) of the IOPR (SDIOPR), IOPR% and SD of the IOPR% (SDIOPR%) were calculated as follows: IOPR = IOPbaselineIOPend point, SDIOPR= (SDbaseline2+ SDend point2 SDbaseline ×SDend point)1/2, IOPR% = IOPR/ IOPbaseline, SDIOPR%= SDIOPR/ IOPbaseline. The difference of IOPR and its SD between groups was then calculated for each individual study.
Description of studies Seventeen potentially relevant controlled clinical trials associated with onesite and twosite phacotrabeculectomy in the treatment of coexisting cataract and glaucoma were identified through the literature search. Among these, four articles without exact raw data available for retrieval according with the exclusion criteria were excluded; two abstract reports were found in the annual meeting abstracts of ARVO; eleven controlled clinical trials that fulfilled the eligibility criteria were included in the present metaanalysis. These were published in 8 different journals in English, Chinese and Spanish and no unpublished data were identified(Table 1).
Efficacy Effect sizes (SMD in patients with onesite and twosite phacotrabeculectomy on IOPR%) from the fixed effects model for all are prospective and retrospective studies, respectively (Figure 1). Twosite phacotrabeculectomy was associated with numerically lower IOPR% relative to onesite in all studies, except for those by Mandic et al and Buys
et al. Both surgical procedures significantly decreased IOP. The pooled summary estimate for all 11 studies favoured
Table 1Characteristics of included studies
Wyse et al1998USAPro16.53375.07/262013
el Sayyad et al1999Saudi ArabiaPro127665.5NA3739
Borggrefe et al1999GermanyPro195074.316/342525
Mandic et al2000CroatiaPro125571.617/222731
Zou et al2001ChinaRetro18.94561.229/162918
IsasiSaseta et al2002SpainRetro63576.416/191916
Dong et al2004ChinaRetro123560.916/191525
Cotran et al2007USAPro367675.426/504343
Buys et al2008CanadaPro247970.929/503940
Nassiri et al2008IranRetro1811368.855/586152
NA: not available.
Figure 1SMD in patients with onesite and twosite phacotrabeculectomy on IOPR%from the fixed effects model.
twosite procedure, and showed twosite phacotrabeculectomy was more effective than onesite in lowering IOP (SMD, 0.19; 95% CI, 0.33 to 0.04; P=0.01). No significant heterogeneity was presented between studies in the onesite versus twosite groups (χ2= 8.86, P=0.55,I2=0.0%). Then, we divided the studies into two subgroups according to study design (prospective and retrospective). Both prospective and retrospective subgroups showed that twosite approach was associated with numerically lower IOPR relative to onesite procedure, but no significant difference was found. There was no significant heterogeneity in these analysis. Publication bias was also tested using the Begg test (P=0.28) and the Egger test (P=0.34), and both produced nonstatistically significant results, providing no evidence of publication bias.
Three studies involving 166 eyes compared onesite with twosite procedure in visual acuity after phacotrabeculectomy (69% onesite and 78% twosite)[7,8,12]. No statistical heterogeneity was observed between studies (χ2= 0.10, P= 0.95,I2=0.0%). The combined result showed there was nonsignificant statistically difference in the percentage having a BCVA of 0.5 or better (OR, 0.65; 95% CI, 0.30 to 1.39, P=0.26).Seven studies, involving 426 eyes, reported the proportions of twosite patients than onesite patients achieved the target IOP without antiglaucoma medication at the end point (73% onesite and 79% twosite)[610,14,15]. No statistical heterogeneity was showed between studies (χ2=8.71, P= 0.19,I2= 31.1%), and the difference between groups was not statistically significant (RR, 0.94; 95% CI, 0.84 to 1.04; P= 0.22).
Tolerability Adverse events in controlled clinical trials comparing between onesite and twosite phacotrabeculectomy are showed in Table 2. Hyphema was one of the most commonly reported postoperative adverse events. However, no
Table 2Adverse events between onesite and twosite phacotrabeculectomy
(n)Crude event rate,n/nOnesiteTwosite
RR (95%CI)HeterogeneityQPI2significant differences comparing between onesite and twosite phacotrabeculectomy were found in the incidence of hyphema, choroidal detachment, hypotony, bleb leak, posterior capsule opacification and shallow anterior chamber, with the pooled RRs being 1.03 (95% CI 0.61 to 1.75), 0.80 (95% CI 0.36 to 1.80), 1.03 (95% CI 0.55 to 1.92), 1.74 (95% CI 0.87 to 3.48), 1.26 (95% CI 0.59 to 2.70) and 0.90 (95% CI 0.27 to 2.95), respectively.
Twosite phacotrabeculectomy now is used frequently as a primary intervention for the management of coexisting cataract and glaucoma. However, it remains controversial as to whether it provides a better outcome than onesite phacotrabeculectomy in the treatment of coexisting cataract and glaucoma. Previous studies have prospectively evaluated the efficacy and tolerability of onesite phacotrabeculectomy compared with twosite procedure[69,14,15]. The overwhelming majority of studies presented that twosite procedure was associated with a numerically lower but nonsignificant reduction in IOP efficaciously compared with onesite approach[68,14]. Variations of sample sizes and followup time within these studies prohibit attribution of treatment outcome to one type of intervention in these reports and make it difficult to draw a valid conclusion regarding the superiority of one procedure over another. We identified various studies that provided comparative treatment outcomes of onesite and twosite procedure and controlled for variations in study characteristics to identify a preferred intervention for the management of coexisting cataract and glaucoma.The results of this metaanalysis imply that, with available evidence from controlled clinical trials, the efficacy of twosite phacotrabeculectomy appears to be superior to onesite for the management of coexisting cataract and glaucoma, and there is nonsignificant difference in tolerability between two surgical procedures. Twosite phacotrabeculectomy was associated with numerically greater, and significant, efficacy than onesite in lowering IOP, numerically greater, but nonsignificant, proportions of twosite patients than onesite patients had a BCVA of 0.5 or better,and numerically greater,but nonsignificant, proportions of twosite patients than onesite patients achieved the target end point IOP. Twosite procedure was comparable with onesite in lowering adverse events. However, the greater IOPR effect and slightly greater BCVA increase effect of twosite procedure over onesite that we have shown does not necessarily indicate a greater surgical effect with twosite procedure. This is because IOP and BCVA merely are surrogate measures for phacotrabeculectomy, and the two surgical procedures may act through pathways independent of this mechanism. There are many preoperative and postoperative key factors to determine which surgical approach to carry out. Factors that may favor a onesite procedure are faster surgical time, less corneal endothelial cell loss, and surgeon experience with a superior approach. Factors that may favor a twosite approach are surgeon familiarity with temporal phacoemulsification, orbital physiognomy, reduced the surgicallyinduced astigmatism, conjunctival scar, limited superior access, ergonomic comfort for the surgeon, and absence of irrigation outflow underneath the conjunctival flap during phacoemulsification that might potentially affect intraoperative antimetabolite effect.
The results of our metaanalysis should be interpreted with caution because there may be some limitations in this metaanalysis. One limitation of our metaanalysis is that the analysis of clinically relevant outcome measures that were based on data pooled from trials and followup periods were not uniform. Another potential source of heterogeneity in the results is the assessment criteria of success. Success was defined as target end point IOP, and there were several different criteria of the normal IOP, such as IOP ≤18, ≤20, and ≤21mmHg. Although such assessments of success are widely used as outcome measures in clinical trials, further research is still needed to fully determine their validity, reliability, and sensitivity to choose the best one. A third limitation of this metaanalysis is that publication bias cannot be excluded fully, because with no sufficient studies, the Begg and Egger tests have a low power to detect publication bias. Finally, some of the controlled clinical trials included in the analysis are not prospective randomized controlled trials, but retrospective or prospective nonrandomized, which may fail to detect actual results. The likelihood of bias was minimized by developing a detailed protocol before initiating the study, by performing a meticulous search for published and unpublished studies, especially published in other languages, and by using explicit methods for study selection, data extraction, and statistical analysis.
In summary, based on the findings of this metaanalysis, we conclude that the efficacy of twosite phacotrabeculectomy appears to be superior to onesite in IOP control, and the proportions of patients in both surgical procedures achieving BCVA of 0.5 or better were comparable, as well as complete success rate. Both twosite and onesite procedure were well tolerated. Pragmatic randomized controlled trials are needed to further evaluate the efficacy and tolerability of twosite phacotrabeculectomy in the treatment of patients with coexisting cataract and glaucoma. In particular, multicenter, longterm, large sample size, randomized, controlled trials are warranted.
1 Shingleton BJ, Pasternack JJ, Hung JW, ODonoghue MW. Three and five year changes in intraocular pressures after clear corneal phacoemulsification in open angle glaucoma patients, glaucoma suspects, and normal patients. J Glaucoma 2006;15(6):494498
2 Tham CC, Li FC, Leung DY, Kwong YY, Yick DW, Lam DS. Microincision bimanual phacotrabeculectomy in eyes with coexisting glaucoma and cataract. J Cataract Refract Surg 2006;32(11):19171920
3 Bayer A, Erdem U, Mumcuoglu T, Akyol M. Twosite phacotrabeculectomy versus bimanual microincision cataract surgery combined with trabeculectomy. Eur J Ophthalmol 2009;19(1):4654
4 Tham CC, Kwong YY, Leung DY, Lam SW, Li FC, Chiu TY, Chan JC, Lam DS, Lai JS. Phacoemulsification versus combined phacotrabeculectomy in medically uncontrolled chronic angle closure glaucoma with cataracts. Ophthalmology 2009;116(4):725731
5 Kobayashi H, Kobayashi K. Randomized comparison of the intraocular pressurelowering effect of phacoviscocanalostomy and phacotrabeculectomy. Ophthalmology 2007;114(5):909914
6 Wyse T, Meyer M, Ruderman JM, Krupin T, Talluto D, Hernandez R, Rosenberg LF. Combined trabeculectomy and phacoemulsification: a onesite vs a twosite approach. Am J Ophthalmol 1998;125(3):334339
7 el Sayyad F, Helal M, elMaghraby A, Khalil M, elHamzawey H. Onesite vs 2site phacotrabeculectomy: a randomized study. J Cataract
Refract Surg 1999;25(1):7782
8 Borggrefe J, Lieb W, Grehn F. A prospective randomized comparison of two techniques of combined cataractglaucoma surgery. Graefes Arch
Clin Exp Ophthalmol 1999;237(11):887892
9 Mandic Z, Ivekovic R, Petric I, ZoricGeber M. Glaucoma triple procedure: a onesite vs a twosite approach. Coll Antropol 2000;24(2):367371
10 Zou Y, Lin Z, Zhou J. Comparison between onesite and twosite incision in phacotrabeculectomy. Chin J Ophthalmol 2001;37(5): 335337
11 IsasiSaseta MB, UrcelaySegura JL, ZamoraBarrios J, OrtegaUsobiaga J, Moreno GarcíaRubio B, CortésValdés C. Trabeculectomy and phacoemulsification. One site vs two site approach. A comparative study. Arch Soc Esp Oftalmol 2002;77(12):677680
12 Dong DQ, Chen G, Hou XW. Clinical observation of the combination of phacoemulsification and trabeculectomy. Chin J Ophthalmol 2004;40(5):295298
13 Shingleton BJ, Price RS, ODonoghue MW, Goyal S. Comparison of 1site vs 2site phacotrabeculectomy. J Cataract Refract Surg 2006;32(5):799802
14 Cotran PR, Roh S, McGwin G. Randomized comparison of 1site and 2site phacotrabeculectomy with 3year followup. Ophthalmology 2008;115(3):447454
15 Buys YM, Chipman ML, Zack B, Rootman DS, Slomovic AR, Trope GE. Prospective randomized comparison of one vs twosite Phacotrabeculectomy twoyear results. Ophthalmology 2008;115(7):11301133
16 Nassiri N, Nassiri N, Rahnavardi M, Rahmani L. A comparison of corneal endothelial cell changes after 1site and 2site phacotrabeculectomy. Cornea 2008;27(8):889894