Chapter 3: Results

	The literature search identified 919 unique, potentially relevant citations to be included in the abstract review.  A summary of the searches completed, strategy used, date of search, number of citations retrieved, and number of unique citations is included as Appendix J.  

	All 919 eligible abstracts were independently reviewed by two members of the study team to determine if they met eligibility criteria.  Disagreements between reviewers about whether to include an abstract or citation were adjudicated at a meeting of the entire study team.  The last electronic search was completed July 18, 2000, and the hand searching and abstract review process ended April 15, 2000.  The abstract review identified 131 citations as eligible for full article review.  Abstracts were deemed ineligible for full article review if they were not applicable to the study questions (1.8 percent of excluded abstracts), if the citation met an exclusion criterion (98 percent of excluded abstracts), or for a combination of the above.  A summary of the reasons for exclusion based on the abstract review may be found in Appendix K.

	At the abstract review level, the citations were tagged as referring to four study topics: development of cataract after glaucoma surgery; acute control of intraocular pressure (IOP) after cataract surgery in glaucoma patients; long-term control of IOP after cataract surgery in glaucoma patients; and preferred surgical technique (including assessment of staged versus combined procedures, efficacy of anti-fibrosis agents in surgical treatment, one- versus two-site surgery, trabeculectomy versus endoscopic laser treatment, and nuclear expression versus phacoemulsification).  The majority of the abstracts (57 percent) were classified as addressing preferred surgical technique  (See Appendix L for a summary of topics.)

	The 131 citations deemed eligible for full article review were reviewed to assess study quality and to extract relevant data.  Of the 131 articles reviewed, 21 (16 percent) were excluded during the full article review (Appendix M), leaving a total of 110 (84 percent) articles for the data extraction.  The reasons for exclusion and number of articles excluded, by reason for exclusion, are listed in Appendix N.  Articles were most frequently excluded because the study was not a controlled trial or a case series of 100 patients or greater, the study did not present original data, or the study did not report outcomes relevant to the study questions.  The next most frequent reason for exclusion was that the article addressed only intracapsular cataract extraction (ICCE).  Figure 2 provides a schematic representation of the results of the literature search, abstract review, and data abstraction process.

Design and Focus of the Studies

	Thirty-three percent of the articles included in this literature review were randomized controlled trials (Evidence Table 1). The remaining studies used non-randomized designs: 35 percent of studies were cohort studies; 21 percent were clinical series; five percent were case- control studies; and six percent were non-randomized controlled trials.

	During the quality assessment, the articles were tagged with regard to the relevant study topic they addressed (see Appendix O for topics assigned during the quality review).  The breakdown of topics addressed is discussed below under Evidence Table 1.  An article may have been judged to contain evidence on more than one topic.  

Results of the Studies

Evidence Table 1:  Overall summary of the literature on treatment of coexisting cataract and glaucoma.

	Evidence Table 1 gives an overview of key features of the 110 studies that were relevant to the study questions and met the inclusion criteria.  The studies are listed in alphabetical order by author so that readers can easily find a given study.  These studies were published between 1980 and April, 2000.  Sixty studies were performed in the United States, 34 studies in Europe, 12 in Asia, and four in other countries.

	Forty-four studies reported on long-term control of  IOP after treatment of patients with coexisting cataract and glaucoma, 15 studies reported on short-term control of IOP after treatment of patients with coexisting cataract and glaucoma, 22 studies reported on cataract development after surgical treatment of glaucoma, 16 studies reported on the efficacy of anti- fibrosis agents in surgical treatment of patients with coexisting cataract and glaucoma, seven studies compared outcomes of single- versus two-site surgery for patients with cataract and glaucoma, 11 studies compared outcomes of nuclear expression versus phacoemulsification for patients with cataract and glaucoma, four studies on compared outcomes of staged versus combined procedures for coexisting cataract and glaucoma, and three studies compared outcomes of trabeculectomy versus endoscopic laser treatment for patients with cataract and glaucoma.	

	Thirty-six of the 110 studies were randomized controlled trials, including six that presented data on long-term control of IOP after treatment of patients with cataract and glaucoma, five that presented data on short-term control of IOP after treatment of patients with cataract and glaucoma, 11 that presented data on cataract development after surgical treatment of glaucoma, 10 that presented data on the efficacy of anti-fibrosis agents in surgical treatment of patients with cataract and glaucoma, four that presented data on outcomes of single- versus two- site surgery for patients with cataract and glaucoma, two that presented data on outcomes of trabeculectomy versus endoscopic laser treatment for patients with cataract and glaucoma, none presenting data on outcomes of nuclear expression versus phacoemulsification for patients with cataract and glaucoma, and none that presented data on outcomes of staged versus combined procedures.  A number of the studies addressed more than one of the study questions.  A summary of key features of the studies reporting on each study question (number of eyes enrolled, mean patient age, proportion of patients African-American, mean length of study followup, and overall study quality) may be found in Appendix P.

Evidence Table 2:  Summary of interventions reported in literature on treatment of coexisting cataract and glaucoma.

	Evidence Table 2 summarizes the treatment interventions used in each study.  For studies of trabeculectomy, the incision location is specified.  For studies involving cataract extraction, the table indicates the type of procedure and the type of incision.  For studies of trabeculoplasty, the table indicates whatever information was available about the wavelength, amount of ciliary processes treated, and power used.  For studies involving endoscopic laser treatment, the degrees of angle treated and laser power are listed.  For studies using anti-fibrosis agents, the table indicates the concentration and duration of mitomycin-C used, the concentration and duration of intraoperative 5-fluorouracil, and the dose and number of injections of postoperative 5- fluorouracil.  Many studies did not report some of these details about the treatment interventions.

Evidence Table 3.  Methodologic quality of literature on treatment of coexisting cataract and glaucoma.

	Evidence Table 3 summarizes the evaluation of the quality of data in the controlled trials and cohort studies that were reviewed. For each study quality category, the score was constructed as the percentage of the total possible points in that domain, ranging from zero percent to 100 percent. An overall quality score was derived from the mean of the quality assessments in the five domains, which were representativeness, bias, description of therapy, outcomes, and statistical analysis. The quality of each study can therefore be assessed both for the individual quality categories, as well as for the overall study quality. In such an assessment, the quality evaluation is limited by the amount and type of data that are given in the report. Hence, the use of published reports has the limitation that the design quality measure consists of both design and reporting elements.

	A total of 131 articles had relevant information and appeared to be eligible for review.  Twenty-one of these articles were excluded during the quality assessment, leaving 110 reports that underwent content assessment. The study designs were classified into five groups: 36 randomized controlled trials (33 percent of the 110), 38 cohort studies (35 percent), 23 clinical series (21 percent), six case-control studies (five percent), and seven non-randomized controlled trials (six percent).

	Study quality category scores were calculated only for controlled trials (randomized and non-randomized) and for cohort studies, comprising 81 articles (74 percent of the 110). The overall quality data divided into study quality category are presented in Appendix Q.  The overall mean quality score was 53 percent, with a range from three to 88 percent. The overall quality score for controlled trials (randomized or non-randomized) was higher than that for cohort studies, with the mean for controlled trials being 59 percent and for cohort studies 46 percent. Scores were higher for the controlled trials in all five categories.

	Among the individual category scores for the 81 articles representing controlled trials and cohort studies, the mean for representativeness of the population was 58 percent, with a range from zero to 94 percent.  Half the studies scored above 63 percent in this domain. For bias, the mean score was 28 percent, the lowest of the domains. Fully 25 of 81 studies (31 percent) had a score of zero, indicating no full randomization, no masking of observers measuring outcomes, and potential for groups to have major differences in key attributes at baseline (or no mention of these important methodological issues in the report). On the other hand, the description of the details of therapy was rated much higher, with a mean score of 65 percent.  The statistics domain category had a mean score of 61 percent.  The quality score for the outcomes category was intermediate at 53 percent.

Evidence Table 4.  What is the effect of cataract surgery (with or without other procedures/treatments) on long-term intraocular pressure control in open-angle glaucoma patients?				

This section reports on the studies addressing long-term IOP control in glaucoma patients undergoing cataract surgery.  Evidence Table 4 and this discussion are limited to articles that are not covered in the later evidence tables.  (However, all studies are summarized in Evidence Tables 1 and 2.)

Cataract Extraction alone versus Cataract Extraction and Glaucoma Procedure

Randomized controlled trials.  There were three randomized trials of good study quality (study quality scores of 67 percent8, 63 percent9, 73 percent10), comparing long-term IOP control in individuals with glaucoma undergoing phacoemulsification cataract extraction to those undergoing phacoemulsification cataract extraction combined with other glaucoma procedures.  Anders and colleagues compared a no-stitch technique employing a radial incision in the base of the scleral tunnel to a scleral phacoemulsification cataract extraction approach.8  At 1 year, the straight phacoemulsification cataract extraction group had a reduction in IOP of 3.7 mm Hg with an average decrease of 0.5 medications.  The combined group had an even larger decrease in IOP (7.70 mm Hg, p < .001) and required 1.5 fewer medications on average.  Twenty-eight of 42 individuals in the phacoemulsification cataract extraction group still required medication at 1 year versus eight of 43 in the combined group.  Storr-Paulsen, Pedersen, and Laugesen compared phacoemulsification cataract extraction to phacoemulsification cataract extraction plus trabeculectomy, but only randomized 10 eyes to each group.10  The median IOP decreased from 23 mm Hg to 16.5 mm Hg in the phacoemulsification cataract extraction group (range 12 to 18 mm Hg) as compared to a decrease from 20 mm Hg to 13 mm Hg (range 12 to 21 mm Hg) in the phacoemulsification cataract extraction plus trabeculectomy group.  The distribution of IOP was not reported.  A study by Gimbel and others compared phacoemulsification to phacoemulsification plus trabeculotomy.9  At 24 months, the mean decrease in the phacoemulsification alone group was 3.8 mm Hg versus 6.1 mm Hg (p = 0.001) in the combined group, but the phacoemulsification alone group was using fewer ocular hypotensive medications (mean of 0.4 versus 1.4).  The results were reported on 51 patients in each group even though 53 were randomized per group.

	Bobrow (quality score 82 percent) reported on patients who were randomized to extracapsular cataract extraction (ECCE) alone in one eye and ECCE plus trabeculectomy in the fellow eye (followed for an average of 87 months).11  Thirty-five patients were randomized to each group.  Eyes randomized to combined procedures had a reduction in IOP of 8.2 mm Hg versus 4.3 mm Hg in the ECCE alone group (p < 0.001).  Individuals in the combined group were taking on average 0.17 medications versus 0.77 in the ECCE alone arm.  No patient required additional surgical procedures to control eye pressure.

Non-randomized studies.  One study (quality score 42 percent) retrospectively reviewed the charts of 21 glaucoma patients undergoing combined phacoemulsification cataract surgery and trabeculectomy and compared the IOP lowering effect in 35 eyes of glaucoma patients who underwent phacoemulsification alone.46  IOP decreased a mean of 3.4 mm Hg in the phacoemulsification cataract extraction alone group as compared to 6.8 mm Hg in the combined group at 6 months with no difference in the number of ocular hypotensive medications being used.

	Conclusion:  Studies comparing cataract extraction alone to cataract extraction and a glaucoma procedure found that while IOP is lowered by cataract extraction alone by about 4 mm Hg, the addition of a glaucoma procedure lowers IOP even more and further may reduce the need for medical therapy.  [Evidence Grade:  A]	

	Two additional randomized trials quality scores 46 percent12 and 45 percent13 looked at aspects of the combined procedure that may influence long-term IOP.  Kim, Jung, and Hwang randomized individuals to phacoemulsification cataract extraction plus either a no-stitch trabeculectomy (11 patients), a T-flap trabeculectomy (eight patients) or a trabeculectomy with sutures (nine patients).12  All three groups had a similar 6 month IOP (around 13 mm Hg), but the group with sutures had a much higher baseline eye pressure.  Conclusions are difficult to draw from this study because of small sample size and large baseline differences between the study groups.  Hugkulstone and colleagues reported on seven eyes undergoing ECCE plus trabeculectomy with a standard intraocular lens (IOL) and nine patients undergoing the same procedure with a heparin-coated IOL at 24 months.13  The mean drop in IOP was 3.8 mm Hg in the standard IOL group and 9.7 mm Hg in the heparin-coated IOL group (p < 0.05).  

	Non-randomized studies.  We found no non-randomized studies addressing this topic.

Limbus- versus Fornix-based Combined Procedures

	Randomized controlled trials.  We found no randomized controlled trials addressing this topic.

	Non-randomized studies.  Four articles of varying quality compared limbus- to fornix- based incisions (study quality scores of 66 percent14, 48 percent15, 41 percent16, and 68 percent17).  Each of the four articles comparing limbus- to fornix-based incisions for combined procedures reported no difference in long-term IOP control using the two approaches.  A study by Murchison and Shields was the only study reporting on ECCE plus trabeculectomy.17  These authors reported no difference in long-term IOP control comparing 22 limbus-based cases to 25 fornix-based cases followed for a mean of 18 months.  The remaining three studies looked at phacoemulsification cataract extraction plus trabeculectomy.  The first study, by Shingleton and colleagues reported on patients undergoing bilateral phacoemulsification cataract extraction plus trabeculectomy.14  First eyes (44) were assigned to limbus-based conjunctival flaps and fellow eyes (44) to fornix-based flaps.  The results were virtually identical in the two groups, with a mean decrease of 6.1 mm Hg.  Studies by Berestka and Brown15 and Tezel and colleagues16 reported on retrospective chart reviews and found similar results in 215 and 45 cases respectively.  Both studies reported a mean decrease in IOP of approximately 8 mm Hg. 

	While the small sample size of the studies makes it unlikely that real differences could be deleted, the very similar IOP results indicate that large differences in effectiveness are unlikely to be present.

	Conclusion:  Limbus- and fornix-based approaches to combined procedures appear to have similar IOP-lowering effects.  [Evidence Grade:  B]

Small versus Large Incision Phacoemulsification Cataract Extraction

	Randomized controlled trials.  We found no randomized controlled trials addressing this topic.

	Non-randomized studies.  Four non-randomized controlled studies of varying quality (study quality scores of 65 percent18, 35 percent19, 58 percent20, and 60 percent21) compared larger versus smaller incisions during combined phacoemulsification cataract extraction plus trabeculectomy procedures.  Lyle and Jin reported a slightly greater decrease in IOP with a 3 mm incision (104 eyes) versus a 6 mm incision (112 eyes) (8.9 mm Hg versus 6.8 mm Hg) but the difference was not statistically significant.18  Wand reported on a study using mitomycin-C and found no significant difference between the two groups (mean decrease in IOP of 7.3 mm Hg in the smaller incision group, (33 eyes) versus 9.1 mm Hg in the larger incision group, (24 eyes).20  The third article, by Kosmin, Wishart, and Ridges found no difference in outcomes comparing small incision surgery using silicone lenses (33 eyes) to larger incision surgery (33 eyes) using poly(methyl methacrylate) (PMMA) lenses (mean IOP decreased 7.7 mm Hg in the small incision group versus 6.7 mm Hg in the larger incision group).21  Vyas and colleagues reported that IOP decreased by 7.6 mm Hg in the small incision group (25 eyes) and 7.8 mm Hg in the larger incision group (25 eyes) at 13 months.19  While the majority were on at least one medication preoperatively, 49 of 50 were taking no medications postoperatively.

	The small sample size of many of these studies means that real differences may have been missed.  However, the results across studies consistently show no difference.

	Conclusion:  Phacoemulsification cataract extraction plus trabeculectomy resulted in a decrease in IOP of about 8 mm Hg with both 3 mm and 6 mm wound sizes.  [Evidence Grade: B]

Phacoemulsification Cataract Extraction plus Trabeculectomy versus Trabeculectomy Alone

	Randomized controlled trials.  We found no randomized controlled trials addressing this topic.

	Non-randomized studies.  Three non-randomized studies (quality scores of 21 percent22, 83 percent23, and 63 percent24) compared IOP results using phacoemulsification cataract extraction plus trabeculectomy to trabeculectomy alone.  Bellucci and colleagues compared 100 trabeculectomies to 200 phacoemulsification cataract extraction plus trabeculectomies and found that trabeculectomy alone resulted in a larger decrease in IOP than the combined procedure (11.2 mm Hg versus 3.1 mm Hg p < .01).22  However, initial IOP was much higher in the trabeculectomy alone group (26.4 mm Hg versus 21.8 mm Hg).  A cohort study by Caprioli and others addressed this question, comparing 40 cases of phacoemulsification cataract extraction plus trabeculectomy (two-site) to trabeculectomy alone.23  These authors reported that IOP decreased more in the trabeculectomy alone group (10.3 mm Hg versus 7.4 mm Hg), and that a higher proportion achieved its target pressure in the trabeculectomy alone group (88 percent versus 72 percent).  Derick, Evans, and Baker reported a slightly larger decrease in IOP in the trabeculectomy alone group (10.6 mm Hg versus 8.9 mm Hg), with similar medication requirements (42 eyes in each group).24

	Conclusion:  Non-randomized studies indicate that phacoemulsification cataract and trabeculectomy combined results in slightly worse IOP control than trabeculectomy alone.     [Evidence Grade:  C]

Phacoemulsification Cataract Extraction plus Trabeculectomy

	Randomized controlled trials.  We identified no randomized controlled trials addressing this question.

	Non-randomized studies.  Seven studies reported on the results of phacoemulsification cataract extraction plus trabeculectomy.25-31  Four studies were case series and so quality scores were not calculated.25-28  The three remaining studies were selected for review because they compared two different approaches to combined phacoemulsification cataract surgery.  These studies provide case series data relevant to the current question, but have fewer than 100 subjects enrolled and therefore may not be as informative.

	With regard to the four large case series, Crandall did not report long-term IOP results, but found that four of 100 eyes (98 Caucasian) required subsequent IOP-lowering surgery.25  Jayamanne, Kostakis, and Phelan followed 100 eyes for a mean of 11 months and found that 96 percent had an IOP less than 21 mm Hg with a mean decrease in IOP of 7.6 mm Hg.26  The third large case series, by Yang and colleagues reported on 182 eyes (12 percent of subjects were African-American), all of whom received mitomycin-C with a mean followup of 17 months.27  The mean IOP decrease was 7.4 mm Hg and 95 percent achieved an IOP less than or equal to 21 mm Hg.  The last case series employed a  no-stitch trabeculectomy combined with a trabeculectomy along with phacoemulsification cataract extraction and reported a mean decrease in IOP of 5.1 mm Hg at 2 years.28

	Arnold compared a no-stitch group (20 eyes) to a two-stitch group (20 eyes) with similar 24 month decreases in IOP (-7.5 mm Hg and -8.0 mm Hg, respectively).29  Patients required virtually no medications, and all patients had an IOP less than or equal to 21 mm Hg.  Crestani and others reported on the effect of phacoemulsification cataract extraction plus trabeculectomy using either a punch or a standard trabeculectomy and found no difference in IOP-lowering at unknown followup (-12.6 mm Hg with the punch versus -14.2 mm Hg with the conventional approach).30  The number of eyes was not reported.  Nielsen compared two techniques of performing phacoemulsification cataract extraction plus trabeculectomy, with one approach reducing IOP by 14 mm Hg (10 eyes) and the other by 8 mm Hg (26 eyes).31

	Conclusion:  Phacoemulsification cataract extraction plus trabeculectomy in these series as well as in the comparative studies discussed above, resulted in an IOP decrease of about 8 mm Hg in individuals followed for a mean of 1 to 2 years.    [Evidence Grade:  C]

ECCE plus Trabeculectomy versus Trabeculectomy

	Randomized controlled trials.  We identified no randomized controlled trials addressing this question.

	Non-randomized studies.  Two cohort studies (quality scores, 49 percent32 and 66 percent33) compared ECCE plus trabeculectomy to trabeculectomy alone.  Naveh and colleagues reported that IOP decreased by 9.8 mm Hg in the combined group (40 eyes) compared to 12.1 mm Hg in the trabeculectomy alone group (38 eyes) at 18 months, with an even greater disparity at the last reported followup (mean of -8.0 mm Hg versus B 14.7 mm Hg).32  The combined group also required an average of 2.1 medications versus 0.5 in the trabeculectomy alone group.  Yu and others also reported greater IOP lowering with trabeculectomy alone (mean of 11.4 mm Hg in 24 eyes) than with a combined procedure (mean of 7.5 mm Hg in 21 eyes) with similar medication use in the two groups.33

	Conclusion:  Trabeculectomy alone appears to lower IOP more than combined ECCE and trabeculectomy.    [Evidence Grade:  B]

ECCE plus TrabeculectomyECCE plus Trabeculectomy

	Randomized controlled trials.  We identified no randomized controlled trials addressing this question.

	Non-randomized studies.  In addition to the two cohort studies sited above, two studies reported on the results of ECCE plus trabeculectomy.  One study was a clinical series and quality scores were not calculated for this study.34  The one remaining study had a quality score of 36 percent.35  In a case series, McCartney and colleagues reported on a mix of 102 open-angle glaucoma (OAG) and angle closure glaucoma (ACG) subjects followed for a mean of 17 months.34  Intraoperative pressure decreased an average of 6.2 mm Hg and medication requirements declined as well.  The other article compared ECCE plus trabeculectomy with and without intraocular lens (IOL) implantation with a mean IOP decline of 6.3 mm Hg in the group with an IOL (23 eyes) followed for an average of 11 months.  

	Conclusion:  ECCE and trabeculectomy combined results in a 6 to 8 mm Hg decline in subjects followed for 1 to 2 years.    [Evidence Grade:  C]

ECCE aloneECCE alone

	Non-randomized studies.  Seven articles reported on the IOP-lowering effect of ECCE alone in glaucoma patients.36-42  Quality scores were calculated for only two articles (40 percent).37  The first article by McGuigan and colleagues reported that all 40 subjects undergoing ECCE had IOP less than 24 mm Hg prior to surgery.37  At an average followup of 18 months, 19 eyes were using the same number of medications, 11 required additional medications and 10 required fewer medications.  Calissendorff and Hamberg- Nystrom reported the results of a case series with 74 remaining subjects followed for 3 years.38  The mean decrease in IOP among 11 ocular hypertensives (who had higher baseline IOP) was 5.5 mm Hg, while among 63 glaucoma patients it was 2.1 mm Hg.  In the third case series, Cinotti and others reported on 160 glaucoma patients undergoing ECCE with a mean followup of 1 year finding a decrease in IOP of 1.4 mm Hg.39  Medication requirements did not change.  Onali and Raitta reported on 37 patients with OAG and 66 with pseudoexfoliation glaucoma with a mean followup of over 2 years.40  IOP declines were similar in the two groups with a mean decrease of 1.5 mm Hg.   Kooner and others reported on 91 ECCE cases in glaucoma patients without prior trabeculectomy.41  With a mean followup of 18 months, IOP decreased an average of 2.2 mm Hg; 81 percent were on the same number of medications, 13 percent were on more medications, and eight percent were on fewer medications at 1 year.  Gunning and Greve looked at 102 with ACG or OAG requiring cataract extraction, including previous filters.42  While the overall IOP lowering was 5.2 mm Hg, the ACG group declined 7.3 mm Hg while the OAG group dropped 2.6 mm Hg.  The final case series reported on twelve eyes undergoing ECCE with IOP implantation with a mean decrease in IOP of 1 mm Hg with over 1 year of followup.36

	Conclusion: ECCE  alone in patients with glaucoma resulted in a modest reduction in IOP (about 1 to 3 mm Hg) at 1-2 years followup, with little change in the use of IOP-lowering medications.    [Evidence Grade:  C]

Phacoemulsification Cataract Extraction AlonePhacoemulsification Cataract Extraction alone

	Non-randomized studies.  In addition to the four controlled trials that included a study group of glaucoma patients undergoing phacoemulsification cataract extraction (PECE) alone, three articles reported the IOP-lowering effect of phacoemulsification cataract extraction alone in patients with glaucoma.43, 44, 45  Study quality scores were calculated for two of the three articles (50 percent43 and 60 percent44).  Hayashi and colleagues reporting on a study from Japan, reported results separately for individuals with ACG  (77 eyes) and OAG (73 eyes).43  At 12 months, the average IOP decreased by 6.4 mm Hg in the ACG group and 4.1 mm Hg in the OAG group.  Shingleton and others reported on glaucoma suspects (75 eyes) and individuals with glaucoma (71 eyes).44  At 1 year IOP decreased a mean of 1.9 mm Hg in the glaucoma suspects and 1.1 mm Hg in those with glaucoma, with glaucoma patients requiring fewer medications.  Perasalo reported on 127 eyes followed up at 1 year and found a mean decrease in IOP of 1.8 mm Hg.45 

	Conclusion: Phacoemulsification cataract extraction alone in glaucoma patients documented a 1 to 4 mm Hg decrease in IOP at 1 to 2 years of followup.    [Evidence Grade:  C]

Cataract Extraction in Patients with a Functioning Filtering Bleb		

	Non-randomized studies.  Five articles looked at the effect of cataract extraction on IOP in patients with preexisting filtering blebs.23, 46, 42, 47   Quality scores are available for two of the four articles (83 percent23 and 37 percent46).  The first article, by Caprioli and colleagues,  reported results of a survival analysis in a matched case-control study comparing individuals with existing blebs (40 eyes) to those with existing blebs undergoing clear cornea phacoemulsification cataract extraction (40 eyes) and found no difference in IOP control over time.23  Chen retrospectively reviewed 115 patients with functioning filtering blebs in whom either ECCE (58) or PECE (57) was performed using both clear corneal and scleral approaches.48  For the group as a whole, 30.4 percent required either additional medication or bleb needling to maintain IOP control at a mean followup of 21 months.  An additional eleven eyes (9.6 percent) required additional glaucoma surgery.  A Cox proportional hazards model found the risk of requiring glaucoma surgery was 3.0 (95 percent confidence interval: 0.7, 12.8) for those undergoing ECCE as compared to PECE.  No control group was enrolled to assess the baseline rate of bleb failure in this population.

	Manoj and colleagues compared ECCE to PECE in patients with preexisting filtering blebs.46  IOP increased significantly (1.9 mm Hg) in the ECCE group (34 eyes), but remained unchanged in the phacoemulsification cataract extraction group (21 eyes).  Medication requirements were also greater in the ECCE group.  Gunning and Greve reported a mean decrease of 1.5 mm Hg (not significant) in individuals undergoing ECCE with preexisting filters.42  Finally, Burratto and Ferrari studied 102 individuals undergoing either ECCE or phacoemulsification with preexisting blebs.47  Although the data presented were limited, it appeared that 8 months after cataract surgery the IOP was similar to baseline.

	Conclusion:  All but one study indicate that cataract extraction (both ECCE and PECE) has a minimal impact on the functioning of preexisting filtering blebs.  The data are insufficient to determine if cataract extraction alters the function of preexisting filtering blebs.    [Evidence Grade: I]

	Other studies.  Other authors reported on unique approaches to the glaucoma patient with cataract.  Montgomery and Gills assessed the IOP-lowering effect of ECCE plus cyclodialysis (238 eyes), reporting that, at a mean of 15 months, 86 percent had Aacceptable@ IOP with 54 percent on no medications.49  Honjo and others (study quality score 13 percent) reported the results of ECCE (25 eyes) or phacoemulsification cataract extraction plus trabeculotomy (22 eyes).50  IOP was lowered in both groups (mean of 9.4 mm Hg in the ECCE group and about 9 mm Hg in the phacoemulsification cataract extraction group) with a mean followup of 29 months.  The PECE group used two different incisions for the trabeculotomy, but results were similar in the two groups.

Evidence Table 5.  What is the effect of cataract surgery (with or without other procedures/treatments) on short-term intraocular pressure control in open-angle glaucoma patients?

	Randomized controlled trials.  There were five randomized trials that reported on short- term IOP control in individuals with glaucoma undergoing cataract surgery.   Quality scores for the studies were good (54 percent51, 73 percent10, 63 percent9, 73 percent52 and 66 percent53).  Three studies compared cataract extraction to cataract extraction plus a glaucoma procedure.51, 10, 9  A study by Krupin, Feitl, and Bishop used an unusual randomization scheme.51  Individuals with controlled glaucoma were randomized to either ECCE or ECCE plus trabeculectomy.  Those with uncontrolled glaucoma were assigned to ECCE plus trabeculectomy or ECCE plus trabeculotomy.  Ultimately, 26 eyes were randomized to ECCE, 33 to ECCE plus trabeculectomy, and nine eyes to ECCE plus trabeculotomy.  The analysis combined the ECCE plus glaucoma surgery groups even though the trabeculotomy results were not as good as those with trabeculectomy.  ECCE alone resulted in a 15.3 mm Hg average increase in IOP with 22 of 26 eyes showing an increase in IOP on postoperative day 1.  The ECCE plus glaucoma surgery groups had a mean decrease of 6.1 mm Hg in IOP with 12 of 42 showing an increase in IOP on postoperative day 1.  

	Storr-Paulsen, Pedersen, and Laugesen compared PECE alone to PECE plus trabeculectomy, but only randomized 10 eyes to each group.10  Timolol was used at the end of surgery and acetazolamide was given 6 hours after surgery.  The median IOP decreased from 23 mm Hg to 20.5 mm Hg in the phacoemulsification cataract extraction group (range 0 to 32 mm Hg) as compared to a decrease from 20 mm Hg to 8 mm Hg (range 0 to 35 mm Hg) in the phacoemulsification cataract extraction plus trabeculectomy group.

	The third study, by Gimbel and colleagues, compared phacoemulsification to phacoemulsification plus trabeculotomy.9  The authors did not report using any ocular hypotensive at the end of the case.  The results at 1 day were similar between the two groups with a mean decrease in IOP of 2.0 mm Hg in the phacoemulsification cataract extraction arm and 2.2 mm Hg in the phacoemulsification cataract extraction plus trabeculotomy arm.  The results were reported on 51 patients in each group even though 53 were randomized per group.

	Conclusion:  There are insufficient data to determine if adding a glaucoma procedure to cataract surgery results in lower IOP than preoperatively or lower IOP than cataract surgery alone 24 hours after surgery.    [Evidence Grade: I]

	The fourth and fifth randomized trials reporting on short-term IOP control assessed medical approaches to prevent IOP spikes in glaucoma patients undergoing ECCE plus trabeculectomy.52,  53  A study reported by Robin demonstrated that apraclonidine given at the end of surgery resulted in lower IOP at 1 day after surgery in individuals undergoing ECCE plus trabeculectomy.52  The group receiving apraclonidine (59 eyes) had a mean decrease in IOP of 12.4 mm Hg versus 0.6 mm Hg in the control group (50 eyes) (all patients were given pilocarpine 2 percent every 6 hours after surgery, and those on beta-blockers prior to surgery continued taking them).

	The fifth study, by West and others compared three treatment arms: acetazolamide alone 1 hour prior to the beginning of the case (10 eyes), miochol intraoperatively (11 eyes), and preoperative acetazolamide and intraoperative miochol (15 eyes).53  Acetazolamide alone and miochol alone both were unable to prevent IOP elevation (mean increase of 8.9 mm Hg and 6.3 mm Hg, respectively), while the combination led to an average decrease in IOP of 0.7 mm Hg on the first day after surgery.

	Conclusion:  Individual studies indicate that apraclonidine or a combination of miochol and acetazolamide blunt the IOP rise in glaucoma subjects undergoing combined ECCE and trabeculectomy who were already on maximal medical management.     [Evidence Grade:  C]

	Non-randomized studies.  The case series and non-randomized studies in this table reported on a wide range of surgical techniques.  Six studies of varying quality (quality scores of 24 percent54, 60 percent21, 41 percent16, 65 percent18, 63 percent24 and 60 percent55) reported the results of PECE on short-term IOP control among glaucoma patients.  Bellucci and Luraschi compared 10 patients in each group receiving either a one- or two-site combined PECE plus trabeculectomy.54  The IOP decrease was greater in the two-site group (mean of 20.6 mm Hg versus 10.5 mm Hg).  Kosmin, Wishart and Ridges compared results using silicone versus PMMA lenses in PECE plus trabeculectomy patients and found a greater decrease in IOP at 1 day using the PMMA lenses (8.7 mm Hg versus 3.4 mm Hg). 21  However, Healon GV was used in silicone cases as opposed to Healon in PMMA cases.  Lyle and Jin compared 3 mm (104 eyes) versus 6 mm (112 eyes) incisions in PECE plus trabeculectomy cases and found similar declines in IOP on postoperative day 1 (mean of 7.8 mm Hg versus 9.9 mm Hg).18  Tezel and others compared limbus (151 eyes) versus fornix-based (64 eyes) flaps in PECE plus trabeculectomy and found a similar immediate decrease in IOP (mean of 7.4 mm Hg versus 7.3 mm Hg).16  The fifth article by Derick, Evans, and Baker found a mean decrease of 6.2 mm Hg with PECE plus trabeculectomy on postoperative day 1.24  Only five out of 42 individuals had an IOP greater than 25 mm Hg.  Finally, Shingleton and colleagues, looked at PECE in glaucoma suspects (75 eyes) and glaucoma patients (71 eyes).44  The IOP decreased a mean of 1.0 mm Hg in the suspects and increased a mean of 1.0 mm Hg in the glaucoma patients (all patients received levobunolol at the end of the case).

	Conclusion:  These articles on PECE in glaucoma patients indicate that combined procedures result in IOP decreases at 1 day postoperatively. [Evidence Grade:  C]

	Conclusion:  Data are insufficient to determine the impact of phacoemulsification cataract extraction alone on short-term IOP control.  [Evidence Grade:  I]

	Four additional articles (with study of quality scores 36 percent56, 40 percent37, 68 percent17 and 30 percent57) addressed the short-term impact of ECCE on IOP in glaucoma subjects.  Vu and Shields found similar IOP rises with ECCE (25 eyes) as with intracapsular cataract extraction (ICCE) (25 eyes).56  McGuigan and colleagues reported a mean IOP rise of 10.2 mm Hg for glaucoma patients undergoing ECCE (80 eyes) whereas nine of 10 patients undergoing a combined procedure had an IOP less than 10 mm Hg on the first postoperative day.37  In a study comparing limbus- (22 eyes) and fornix-based flaps (25 eyes), Murchison and Shields found that a slightly higher proportion undergoing the limbus-based procedure had a decrease in IOP (100 percent versus 76 percent).17  McKinzie and Boggs compared intracameral acetylcholine (8 eyes) to intracameral carbachol (8 eyes) at the end of the case and found that IOP increased by 16.4 mm Hg in the acetylcholine group while it decreased by 0.1 mm Hg in the carbachol group.57

	Conclusion:  Combined ECCE and trabeculectomy results in lower IOP on the first postoperative day.  [Evidence Grade:  C]

	Conclusion:  ECCE alone in glaucoma patients appears to increase IOP on the first postoperative day. [Evidence Grade:  C]

Evidence Table 6.  What is the effect of glaucoma surgery on development and progression of cataract?

	Randomized controlled trials.  Two recent randomized controlled trials suggest that glaucoma surgery is associated with higher rates of development and progression of cataract.  Persons randomized to have IOP lowered by 30 percent from baseline in the Collaborative Normal Tension Glaucoma Study (study quality score of 67) many of whom received incisional glaucoma surgery, had an incidence of cataract (23 of 61, or 38 percent) which was significantly greater than for the group not randomized to undergo pressure reduction (11 of 79, or 14 percent, p = 0.0075).58, 59   Likewise, in the Advanced Glaucoma Intervention Study (study quality score of 70 percent), the rate of cataract operations among black subjects randomized to trabeculectomy first (TAT) (34.6 percent) was significantly (p < 0.001) higher than among black subjects randomized to receive argon laser trabeculoplasty first (ATT) (22.5 percent).60  Although the cumulative probability of cataract surgery for white patients randomized to TAT (37.1 percent) was also higher than for ATT (29.7 percent), the difference was not statistically significant (p = 0.097).

	Non-randomized studies.  Quality scores were not calculated for eight of the non- randomized studies reporting data relevant to this question.61-68  The studies for which quality scores were determined were of varying quality (43 percent69, 75 percent70, 73 percent71, 85 percent72, 35 percent73, 75 percent74 and 22 percent75).  In a non-randomized trial in India, in which a subject’s eye with higher IOP received trabeculectomy and the other eye medications, Dastur reported that 12 of 70 eyes required cataract extraction within 3 years after trabeculectomy, whereas no cataract surgery was performed in the medically treated eyes.69

	In a prospective study of visual acuity loss after trabeculectomy involving 508 eyes of 440 patients, Costa reported lens opacification as the leading cause of two or more lines of vision loss in this group.61  Cataract progression/formation was also the most common postoperative complication (20 percent), and the leading cause of postoperative vision loss in Cheung's series of 157 trabeculectomies with mitomycin-C.62  In his clinical series of trabeculectomies, Watson found presence of cataract prior to glaucoma surgery to be the major determinant of increase in cataract.63  Cataract was not related to preoperative IOP, reduction in IOP, operative complications other than flat chamber with corneal touch, the type or frequency of preoperative medicines, or the type of glaucoma.  Tornqvist64 found a doubling of the visual angle due to 

cataract in 37 percent of persons after trabeculectomy after 5 years, while Jerndal65 found that 10 percent of subjects required cataract extraction after trabeculectomy over a similar period of followup.

	Lamping and colleagues reviewed 181 eyes that underwent full-thickness glaucoma and 71 eyes undergoing trabeculectomy that had at least 2 years follow-up.69 they found that cataract extraction was performed in 34 percent of full thickness procedures and in 21 percent of the trabeculectomies, a difference that was of borderline statistical significance (p = 0.06).  Although the amount of cataract surgery seems to exceed that which would have occurred in eyes no undergoing glaucoma surgery, the lack of a control group not undergoing surgery prohibits drawing firm conclusions.

	Several of the reviewed studies considered other factors associated with glaucoma surgery which might increase the risk of lens opacity.  In his randomized trial of mitomycin-C concentration and duration in India, Robin reported no eyes with a 2-line decrease in vision or requiring cataract surgery among subjects randomized to receive trabeculectomy with placebo, while the age-adjusted relative risk for progression of cataract was highest in the two groups receiving the highest doses of mitomycin-C: 0.4 mg/ml for 2 minutes (relative risk 2.17, 

p = 0.09) and 0.2 mg/ml for 4 minutes (relative risk 3.18, p = 0.01).70  Kitazawa found cataract progression (18 percent) exclusively in subjects randomly allocated to receive mitomycin-C (0.2 mg), with no lens change reported in those receiving a 10-fold lower dose.71  This small trial included a total of 19 eyes.  Rates of cataract progression did not differ significantly between subjects randomized to receive a mitomycin-C concentration of 0.4 mg/cc (three of four) and those receiving 0.2 mg/cc (four of five), in a small trial reported by Sanders and colleagues.72  Similarly, no difference in rate of cataract progression was reported between patients randomized to daunorubicin (three of 13) and those treated with 5-fluorouracil (three of 14) in Demailly's randomized trial.73

	Asamoto reported significantly higher rates of anterior subcapsular cataract among subjects undergoing trabeculectomy in which the anterior chamber was reformed with air, as opposed to balanced salt solution (BSS), sodium hyaluronate, or spontaneous reformation.66  There were 11 permanent cataracts in eyes reformed with air, but only two were visually significant, and only one required surgery.

	Other surgical treatments for glaucoma are also associated with postoperative cataract although controlled data do not generally exist to demonstrate whether this risk is increased compared to non-operated subjects.  Progression of cataract was reported in seven percent of subjects after deep sclerostomy with collagen implant after a mean 18 month followup by Karlen.67  The rate of cataract progression varied between two to four percent after adult trabeculotomy in two studies reported by Tanihara.68  Three eyes receiving argon laser trabeculoplasty underwent cataract extraction, as compared to one (3 percent) in a small, controlled, retrospective study by Tuulonen.76  Higher rates of cataract were reported in association with full thickness glaucoma surgeries as opposed to trabeculectomy by Wilson77, Lewis78, and Blondeau.74  Spaeth found roughly equivalent rates of cataract progression between the two procedures in a smaller (n=15) study.75

	Glaucoma surgery appears to be associated with increased risk of postoperative visually significant cataract, which may require cataract surgery.  The risk of postoperative cataract may be increased with age, use of mitomycin-C, intraoperative use of air to reform the anterior chamber, postoperative flat chamber, and full thickness glaucoma surgery.

	Conclusion:  Glaucoma surgery is associated with increased risk of postoperative cataract.  [Evidence Grade:  A]

Evidence Table 7.  What is the effect of mitomycin-C on intraocular pressure control after combined cataract and glaucoma surgery?

	Randomized controlled trials.  The overall quality of these studies (mean score 59 percent, range from 48 percent to 67 percent) exceeded those of the average study in this report (mean score 53 percent).  

	Three groups have conducted randomized controlled trials evaluating the effect of mitomycin-C in combined cataract and glaucoma surgery.79-83  Cohen and colleagues, performed a study (72 eyes total) using a high dose of mitomycin-C (0.5 mg/ml for 2.5 minutes) versus placebo at the time of phacoemulsification and trabeculectomy.79  They found that at 12 months, with data for 52 eyes, the mitomycin-C group had greater IOP lowering (mean of 7.7 mm Hg versus 3.1 mm Hg, p=0.001), was on fewer medications (mean of 0.6 versus 1.4 per eye, p=0.012), and had larger filtration blebs.  Carlson and others, performed a smaller study (29 eyes total), also using a high dose of mitomycin-C (0.5 mg/ml for 3.5 minutes) versus placebo at the time of phacoemulsification and trabeculectomy.80  At one year, the IOPs were lower (mean of 5.6 versus 2.6, p=0.11) and fewer eyes needed medications (zero of 14 eyes versus five of 15 eyes, p=0.04) in the mitomycin-C group than in placebo group.  Throughout the course of the study, eyes treated with mitomycin-C had an IOP that averaged 3 mm Hg less than the placebo- treated eyes (p=0.04).  

	Shin’s group conducted a number of studies on this topic.81-83  Unlike the other studies, their trials included a significant proportion of African-Americans.  There may be some overlap in the eyes reported in their papers.  The authors distinguished between eyes without previous glaucoma surgery, and those with previous glaucoma surgery.

	In the largest study by Shin and colleagues, 96 eyes without previous glaucoma surgery received mitomycin-C 0.5 mg/ml for varying lengths of time at the time of combined phacoemulsification and trabeculectomy and 101 eyes without previous glaucoma surgery received placebo.82  Using life table analysis, no difference (p = 0.12) was found in the success rate of glaucoma surgery between the eyes receiving mitomycin-C (approximately 65 percent at 2 years) and those receiving placebo (approximately 50 percent at 2 years).  However, there was a trend for greater success (65 percent) at 30 months in the mitomycin-C treated group than in the control group (50 percent).  Using life table analysis mitomycin-C improved the success rate in subgroups including eyes of African-Americans (p = 0.007), in eyes on two or more glaucoma medications (p = 0.018) and in eyes with IOP of 20 mm Hg or greater (p = 0.006).

	In a second randomized trial from Shin's group, Lemon and colleagues randomized 69 eyes without previous glaucoma surgery receiving 0.5 mg/ml of mitomycin-C for only 1 minute at the time of combined phacoemulsification and trabeculectomy to either a fornix- or limbus- based conjunctival flap, and found no difference in IOP lowering (mean 3.3 mm Hg) or complications between the two groups.83 

	In a third study, Shin, Kim, Shoth and colleagues, randomized eyes with primary open- angle glaucoma (POAG) and failed previous glaucoma filtration surgery to phacoemulsification and trabeculectomy with or without mitomycin-C (0.5 mg/ml for one minute).81  Using life table analysis, the use of mitomycin-C appeared to increase the success rate of surgery (p = 0.02).  At 14 months, for example, the success rate was approximately 60 percent in the mitomycin-C treated group and 25 percent in the control group.

	Non-randomized studies.  Budenz and colleagues in a study comparing 5-fluorouracil, mitomycin-C, and no anti-fibrosis agent, failed to find a significantly greater degree of IOP lowering in eyes that received mitomycin-C at the time of phacoemulsification and trabeculectomy (mean 4.6 mm Hg) than in those receiving no anti-fibrosis agent (mean 3.4 mm Hg).84  Their results are difficult to interpret because the IOP fell less in the 5-fluorouracil group than in the group that did not receive an anti-fibrosis agent.  The number of medications required after surgery was not significantly different between the mitomycin group (mean 0.4) and the no anti-fibrosis group (mean 0.7).  However, overall the mitomycin-C group had lower IOP and required fewer medications.

	Liu and colleagues in Taiwan compared 22 eyes that underwent combined phacoemulsification and trabeculectomy with 0.2 mg/ml mitomycin-C for 3 minutes to 18 eyes that did not receive mitomycin-C at the time of combined cataract and glaucoma surgery.85  The IOP at 1 year was lower in the mitomycin-C group (mean 10.9 mm Hg versus 14.6 mm Hg, p=0.004), but because the mitomycin-C group had a lower preoperative IOP (mean 16.1 mm Hg versus 18.7 mm Hg), the decrease in IOP was only slightly greater in the mitomycin-C group, (mean 5.16 mm Hg versus 4.14 mm Hg for the controls).  The authors did not indicate whether this difference was statistically significant.

	El-Sayyad and colleagues compared combined phacoemulsification and cataract extraction with mitomycin-C to trabeculectomy with mitomycin-C followed at a later date by phacoemulsification (mean delay 3.2 months).86  In both instances, the IOP fell by a mean of greater than 13 mm Hg. 

	Shin, Kim, Ren and colleagues evaluated the incidence of posterior capsular opacification in eyes without previous glaucoma surgery receiving mitomycin-C or placebo at the time of combined phacoemulsification and trabeculectomy.87  Using life table analysis they found that YAG capsulotomy was performed less frequently in the eyes that received mitomycin-C (p = 0.004).  For instance, the proportion of eyes receiving capsulotomy by 4 years after surgery was approximately 60 percent in the  placebo group and 40 percent of the mitomycin-C group.

	In summary, the literature suggests that overall, the use of mitomycin-C in combined procedures results in lower IOP.  Two fairly high quality randomized controlled trials found an IOP-lowering effect of mitomycin-C.  A larger, high quality study (and the only one with a significant number of African-Americans) failed to find an overall effect, but did demonstrate an effect when important subgroups were analyzed.87   No serious side effects attributable to mitomycin-C have been seen, and it may reduce the rate of posterior capsular opacification.

	Conclusion:  Overall, the use of mitomycin-C in combined cataract and glaucoma surgery results in lower IOP.    [Evidence Grade: B]

Evidence Table 8.  What is the effect of 5-fluorouracil on intraocular pressure control after combined cataract and glaucoma surgery?

	Randomized controlled trials.  There were four randomized controlled trials reporting the effect of 5-fluorouracil in combined cataract and trabeculectomy surgery.88-91  The mean overall quality score of these studies (48 percent) was close to the score for all the randomized trials evaluated in this report (53 percent).  In two studies, ECCE was used.  In the first study, in a largely African-American population, Hennis and Stewart randomized 32 eyes undergoing combined ECCE and trabeculectomy to receive up to 14 daily injections of 5-fluorouracil or not.88  With short followup of 3 months, no difference could be detected in IOP (power of finding a 4 mm difference of 92 percent), number of glaucoma medications, or bleb appearance between the two groups.  In a second study, Wong and colleagues randomized 24 predominantly Caucasian patients to receive five injections of 5 mg during the first 2 postoperative weeks and 20 patients to not receive 5-fluorouracil.89  IOP was lowered by a mean of 4 mm Hg in both groups, and there were no important differences between them.  The authors did not comment on the study's power to detect a difference between the two groups.

	Phacoemulsification combined with trabeculectomy was used in the other two randomized controlled trials.  O'Grady and others, in a predominantly African-American population, randomized 74 patients to either receive or not receive 5-fluorouracil (mean of 5 injections of 5 mg during the first week after surgery) following single-site combined  phacoemulsification and trabeculectomy.90  No beneficial effect of 5-fluorouracil was seen (p values at all time points >0.05, but no power calculations were reported).  In an Italian population, Gandolfi and Vecchi randomized 24 eyes undergoing a limbus-based trabeculectomy and clear corneal phacoemulsification to receiving 5 once-weekly injections of 

5 mg of 5-fluorouracil.91  At 1 year, 10 of 12 eyes in the 5-fluorouracil group had IOPs of 15 mm Hg or less compared to one of 12 in the control group (p=0.001, Fisher's exact test), suggesting that 5-fluorouracil injections were beneficial.

	Non-randomized studies.  Budenz and others compared the results of eyes undergoing trabeculectomy and phacoemulsification and receiving either mitomycin-C, 5-fluorouracil injections, or no anti-fibrosis agent.84  The 5-fluorouracil doses were not standardized.  At 1 year, the mean IOP lowering was 2.7 mm Hg in the 5-fluorouracil group and 3.4 mm Hg in the control 

group.  The authors concluded that 5-fluorouracil was not beneficial in combined phacoemulsification and trabeculectomy.

	Cohen and others also compared the results of eyes randomized to either receive or not receive 5-fluorouracil at the time of combined cataract and glaucoma surgery.92  Some eyes had undergone previous glaucoma surgery, and the techniques for cataract surgery varied.  A mean of 17 mg 5-fluorouracil was administered during the first 2 postoperative weeks.  The mean fall in IOP with about 6 months followup was 4.5 mm Hg in the control group and 4.1 mm Hg in the group receiving 5-fluorouracil.

	Hurvitz compared 38 eyes receiving 5-fluorouracil and combined phacoemulsification and trabeculectomy with 55 eyes that underwent the same procedure, but without 5- fluorouracil.93  At 1 month the IOP was a mean of 1.9 mm Hg lower in the phacoemulsification/5-fluorouracil group than in the phacoemulsification alone group (p=0.08).  At 1 year, the decrease in IOP was slightly greater (mean of 6.2 mm Hg) in the group receiving 5-fluorouracil than in the group not receiving 5-fluorouracil (mean of 5.3 mm Hg) (no statistical analysis provided).

	Donoso and Rodriguez compared the results of single incision, combined trabeculectomy and phacoemulsification with that of a matched group of eyes undergoing phacoemulsification after trabeculectomy.94  In both groups, a single intraoperative application of 5-fluorouracil, 50mg/ml, was given.  The final intraocular pressures were the same in both groups (mean of 12.6 mm Hg in the sequential group versus 12.2 mm Hg in the combined group, p=0.64).

	In summary, except for the one study from Italy91, which differed from all other studies in the use of a two-site phacoemulsification procedure, no method of administration of 5- fluorouracil appeared to enhance the IOP lowering effect of combined cataract and glaucoma surgery.

	Conclusion:  5-fluorouracil does not improve the IOP lowering effect of combined cataract and glaucoma surgery.    [Evidence Grade:  B]

Evidence Table 9.  Which cataract or combined procedure techniques lower intraocular pressure the most?

One- versus Two-SiteOne- versus Two-Site

	Randomized controlled trials.  Three randomized controlled trials of better than average overall quality (quality scores 64 percent95, 61 percent96 and 60 percent97) and one of lesser quality (quality score of 11 percent98) were reviewed.

	In a German study, Borggrefe and others compared the results of single- versus two-site phacoemulsification and trabeculectomy, without anti-fibrosis agents, in eyes without prior incisional surgery.95  They found marked intraocular pressure lowering (mean of 13 to15 mm Hg) with greater than 1 year followup in both groups.  The IOP reduction was 50 percent in the two-site group and 43 percent in the one-site group, a difference that was not statistically significant (p=0.262).  There were no important differences in outcomes between the two groups. 	

	In a Saudi Arabian study, El-Sayyad and colleagues randomized 76 eyes to either one- or two-site phacoemulsification and trabeculectomy, with the use of mitomycin-C.96  At 1 year, they found that both techniques effectively lowered IOP.  The IOP lowering was slightly greater in the two- (mean 11.0 mm Hg) compared to the one-site (mean 7.1 mm Hg) group (no statistical analysis of IOP was provided by the authors), but the two-site group was also taking slightly more medication (mean 1.9 versus 1.6, p=0.6).  Eighty-seven percent of the eyes in the two- and  84 percent in the one-site group had IOP less than or equal to 21 mm Hg without medications (p=0.47).

	In a study from Italy, Rossetti and colleagues randomized 50 eyes to one- or two-site phacoemulsification and trabeculectomy, without the use of anti-fibrosis agents.98  IOP was lowered by a mean of 9.4 mm Hg in the one-site group and 11.0 mm Hg in the two-site group.  Whether this small difference, which was not subjected to statistical analysis, was attributable to the operative technique or to baseline differences between the two groups cannot be determined.

	In the United States, Wyse and colleagues randomized patients to single- versus two-site surgery using mitomycin-C 0.4 mg/ml for 2 minutes.97  With greater than 1 year followup, they found a slightly greater lowering of IOP (31 percent) in the two-site group than in the one-site group (23 percent, p=0.294), and a  greater need for medications in the single-site group (mean of 0.9 medications per eye versus 0.2 medications per eye, p=0.03).

	Non-randomized studies.  For the non-randomized studies, quality scores tended to be low (24 percent54, 28 percent99, and 31 percent100).  Bellucci and Luraschi performed two-site surgery in 10 patients and one-site surgery in 10 patients.54  The IOP lowering effect was similar in both groups, but the one-site group required more medication.  The lack of randomization and the small number of patients precludes drawing firm conclusions from the data.

	In a European population, Anand and colleagues compared three techniques:  ECCE with nuclear expression and trabeculectomy through a single limbal site, ECCE with nuclear expression through clear cornea and trabeculectomy through a second site, and phacoemulsification and trabeculectomy through a single limbal site.99  No differences in IOP lowering were noted among the three groups (p=0.90 by analysis of variance).

	Gayton and others compared 50 eyes undergoing one-site combined surgery with 65 patients undergoing two-site surgery.100  Mitomycin-C was used in some cases.  The authors state that there were no significant differences at any time period in the amount of IOP lowering between the two groups.

	In summary, although none of the four randomized controlled trials demonstrated a statistically significant difference in IOP lowering between one- and two-site surgery, they all showed a trend toward either lower IOP and/or reduced glaucoma medications in two-site surgeries.

	Conclusion:  Two-site combined trabeculectomy and cataract extraction may provide slightly lower IOP than one-site surgery.    [Evidence Grade: C]

Nuclear Expression versus PhacoemulsificationNuclear Expression versus Phacoemulsification

	Randomized controlled trials.  We found no randomized controlled trials addressing this question.

	Non-randomized studies.  Six studies reported a greater IOP reduction in eyes undergoing phacoemulsification combined with trabeculectomy than in eyes undergoing nuclear expression combined with trabeculectomy and three studies found no difference.  The mean overall quality score of these 9 studies was 42 percent (quality scores 50 percent101, 46 percent102, 38 percent103, 43 percent104, 33 percent93, 54 percent105, 36 percent107, 28 percent99, and 50 percent106). 

	In Australia, Chia and Goldberg compared 50 eyes that underwent phacoemulsification and trabeculectomy with 50 that underwent ECCE with nuclear expression; 5-fluorouracil was used in both groups.101  With 1 to 2 years followup, the IOP lowering was greater (mean 5.8 mm Hg) in the phacoemulsification group than in the ECCE group (mean 2.5 mm Hg) and there were fewer complications.  Shingleton and colleagues compared 35 eyes undergoing ECCE with nuclear expression and trabeculectomy with 37 eyes undergoing phacoemulsification and trabeculectomy.102  Phacoemulsification resulted in slightly greater IOP lowering (mean 5.4 mm Hg) than ECCE with nuclear expression (mean 3.2 mm Hg).  Tezel and colleagues compared 127 eyes undergoing combined surgery with ECCE (nuclear expression) with 270 eyes undergoing combined surgery with phacoemulsification.103  Both groups received mitomycin-C, 0.2 mg/ml for 2 minutes.  With 12 to 24 months followup, IOP was lowered a mean of 6.5 mm Hg in the ECCE group and 7.9 mm Hg in the phacoemulsification group.  Wedrich and colleagues compared 54 eyes undergoing ECCE with nuclear expression and trabeculectomy with 49 eyes undergoing phacoemulsification with trabeculectomy.104  With a followup of at least 24 months, IOP was lower in the phacoemulsification group.  Within a study primarily designed to evaluate the effect of 5-fluorouracil upon combined cataract and glaucoma surgery, Hurvitz compared the results of 55 eyes undergoing phacoemulsification and cataract surgery without anti-fibrosis agent with 36 eyes undergoing ECCE with nuclear expression and cataract surgery without anti-fibrosis agent.93  IOP was lowered a mean of 3.4 mm Hg in the nuclear expression group and 5.3 mm Hg in the phacoemulsification group.  However, possible selection biases and the surgeon’s learning curve could account for the greater effect observed in the phacoemulsification group.  Wishart and Austin in England compared 34 eyes that underwent trabeculectomy and phacoemulsification with the previous 34 combined cataract and glaucoma operations that they performed by ECCE (nuclear expression).105  The IOP was lowered at 1 year by a mean of 8.6 mm Hg in the phacoemulsification group and by 5.2 mm Hg in the ECCE (nuclear expression group).  

	Three studies reported no difference in IOP reduction in eyes undergoing phacoemulsification combined with trabeculectomy compared to eyes undergoing nuclear expression combined with trabeculectomy.  In a European population, Anand and others compared three techniques:  ECCE with nuclear expression and trabeculectomy through a single limbal site, ECCE with nuclear expression through clear cornea and trabeculectomy, and phacoemulsification and trabeculectomy through a single limbal site.99  No differences in IOP lowering were noted among the three groups.  Posterior capsular opacification requiring capsulotomy was less common in the phacoemulsification group.  In England, Kosmin and others compared 32 eyes undergoing ECCE with nuclear expression and trabeculectomy with 31 eyes undergoing phacoemulsification and trabeculectomy.106  With greater than 2 years followup, there was little difference in the amount of IOP lowering or need for glaucoma medications.  Stewart and colleagues compared the results of trabeculectomy and phacoemulsification in 16 eyes with trabeculectomy with ECCE (nuclear expression) in 14 eyes with followup of 1 year.107  No significant differences were found between the two techniques, although the study was very small.

	Manoj and colleagues, in England, studied a related question:  whether ECCE with nuclear expression or phacoemulsification provided better IOP control when cataract extraction was performed in eyes with prior trabeculectomy.47  Phacoemulsification appeared to be better than nuclear expression in terms of IOP and need for IOP lowering medications at 2 years, but possible baseline differences between the two groups complicates interpretation of the results.

	Honjo and colleagues, performed a unique study comparing three methods of combining cataract extraction with trabeculotomy (rather than trabeculectomy).50  Twenty-five eyes underwent nuclear expression, 10 eyes single-site surgery with phacoemulsification, and 12 eyes two-site surgery with phacoemulsification.  The nuclear expression group had a mean IOP lowering of 9.6 mm Hg on 1.1 medications; the two-site phacoemulsification lowered IOP by a mean of 7.4 mm Hg on 0.6 medications, and the one-site phacoemulsification lowered IOP by 11.6 mm Hg on 1.4 medications.  Thus there appeared to be little difference between the techniques.  However, the baseline characteristics of the groups were not well characterized, and the number of subjects was small.

	In summary, although no randomized controlled trials on this topic were performed, the preponderance of studies find that IOP is lower in eyes undergoing phacoemulsification rather than nuclear expression when combined with trabeculectomy.

	Conclusion:  IOP is lowered more when phacoemulsification rather than nuclear expression is used in combined cataract and glaucoma surgery.    [Evidence Grade:  C]

Evidence Table 10.  Is intraocular pressure lowered more by a staged glaucoma and cataract surgery or by simultaneous cataract and glaucoma surgery?

	Randomized controlled trials.  We found no randomized trials addressing this issue.

	Non-randomized studies.  Quality scores were calculated for only one of the non- randomized studies addressing this question.  Donoso and Rodriguez compared the results of single incision, combined trabeculectomy and phacoemulsification with that of a matched group of eyes undergoing phacoemulsification after trabeculectomy.94  In both groups, a single intraoperative application of 5-fluorouracil, 50 mg/ml, was given.  The final intraocular pressures were the same in both groups.

	El-Sayyad and colleagues matched 53 consecutive eyes undergoing simultaneous phacoemulsification and trabeculectomy with mitomycin-C through a single site with 53 eyes that underwent trabeculectomy with mitomycin-C followed at a later date by phacoemulsification.86  In the latter group, the phacoemulsification was through clear cornea in 32 eyes and at the limbus in 21 eyes.  Both protocols yielded similar and marked IOP reductions.

	Murchison and Shields compared three surgical approaches in patients with coexisting cataract and glaucoma.108  Two of these approaches, simultaneous glaucoma and cataract surgery, and filtering surgery followed by cataract surgery, bear directly on the question of interest.  Twenty-two eyes with compelling reasons to undergo simultaneous cataract and glaucoma surgery, that underwent a combined guarded filtering procedure, were compared to 22 eyes whose most pressing problem was IOP control requiring filtration surgery, that underwent first filtration surgery alone, and then cataract surgery at a later date.  The cataract surgery technique was ECCE with nuclear expression; the filtering procedure was either trabeculectomy or a full thickness procedure.  The final IOP at 12 to 24 months was similar in the two groups, although the eyes undergoing the staged procedure had much higher IOPs to begin with.  Only 14 percent of eyes undergoing the combined procedure had an increase in IOP in the first 2 postoperative days compared to preoperatively.  This study is difficult to interpret because the two groups differed so markedly in their characteristics.	

	In summary, three studies, none of them randomized, directly compared staged versus combined procedures.  Within this limited database, the overall outcome of combined cataract and glaucoma surgery, whether employing nuclear expression or phacoemulsification, and regardless of anti-fibrosis regimen, appears to be similar for staged and combined procedures.

	Caprioli and colleagues, carefully matched 40 consecutive eyes undergoing temporal corneal phacoemulsification following trabeculectomy with 40 eyes that had undergone trabeculectomy but did not have subsequent cataract surgery.108  The survival curves for IOP control were the same for both groups of eyes, suggesting that the cataract surgery did not adversely affect IOP.  Although not directly addressing the question of whether combined procedures or staged procedures are preferable, the inference is that IOP can be effectively lowered by a staged procedure.

	Conclusion:  There is insufficient evidence to conclude that staged or combined procedures give better results.    [Evidence Grade:  I]

Evidence Table 11.  Does trabeculectomy combined with cataract surgery or another operation combined with cataract surgery lower intraocular pressure more?

	Randomized controlled trials.  Gayton and colleagues (study quality score 51 percent), performed a randomized controlled trial of trabeculectomy versus endoscopic laser cycloablation, each combined with cataract surgery, in 58 eyes.110  The combined procedures using trabeculectomy used a two-site approach, and some eyes received mitomycin-C.  With a mean followup of 2 years, eyes receiving trabeculectomy had a greater reduction of IOP (mean 10.6 mm Hg) than those receiving endolaser (mean 7.3 mm Hg).

	Gianoli, Schnyder, Bovey et al. (study quality score 59) randomized 60 eyes of 60 patients to receive either combined phacoemulsification and deep sclerectomy or combined phacoemulsification and trabeculectomy.111  The former procedure was performed as a two-site operation, the latter as single-site.  At 12 months the IOP was lowered by 10.9 mm Hg in the deep sclerectomy eyes and by 9.89 mm Hg in the trabeculectomy eyes, a non-significant difference.  The IOPs at entrance were similar in the two groups (24.8 mm Hg in the deep sclerectomy group and 24.6 mm Hg in the trabeculectomy group) as were the number of post- operative glaucoma medications (0.6 in both groups).  It should be noted that data on the number of eyes remaining in the study at the postoperative time points was not provided and the two groups differed not only in glaucoma procedure but in one- versus two-sites.

	Non-randomized studies.  Kendrick and others (quality score 20), reported a cohort study comparing ab interno laser thermal sclerostomy combined with cataract surgery versus trabeculectomy combined with cataract surgery.112  At 6 months they found a mean IOP lowering of 5.2 mm Hg in the laser thermal sclerostomy group and 2.3 mm Hg in the trabeculectomy group.  Problems with comparability of the two groups limited the validity of the results.

	In summary, few trials of other techniques besides trabeculectomy have been reported in combined cataract and glaucoma operations.  One study does suggest comparable IOP lowering effects of deep sclerectomy and trabeculectomy when combined with phacoemulsification. Further research will be necessary before other glaucoma procedures replace trabeculectomy in combined cataract and glaucoma operations.

	Conclusion:  There is insufficient evidence to compare the effectiveness of alternative glaucoma procedures to trabeculectomy in combined procedures.    [Evidence Grade:  I]

Evidence Table 12.  What are the reported complications of treatment for coexisting glaucoma and cataract?

	Of the 110 reports of trials included in the review, only 92 studies reported data on complications.  The complications were divided into those that occur soon after surgery (early) and late complications, defined typically as more than 1 month after surgery.

Early Complications

	Rupture of the posterior capsule of the lens is an intraoperative complication that makes implantation of an artificial intraocular lens more difficult and increases the probability of other complications, some of which are vision-threatening.  Overall, the rates of capsule rupture in these reports were modest and not dramatically different with rates for persons undergoing cataract surgery who do not have glaucoma, averaging less than five percent of eyes.  Two reports, Berestka and Brown15, and Murchison and Shields17 documented substantially higher capsule rupture in eyes undergoing combined trabeculectomy/lens implant surgery when a limbus-based conjunctival flap was used (18 percent in each series) compared to eyes in these series that had fornix-based flaps.

	Early leakage of the wound in the area of a trabeculectomy bleb occurred in zero to 10 percent of operations in a variety of settings.  Some reports documented higher rates when certain surgical techniques were used.  Wong and colleagues found 25 percent leakage when 5-fluorouracil was used in conjunction with cataract/trabeculectomy surgery compared to eight percent leakage without  5-fluorouracil.89  Cohen found 5-fluorouracil usage associated with 59 percent early leakage compared to 19 percent without it.92  It is intuitively consistent that anti- fibrosis treatment (5-fluorouracil) would slow healing and lead to early leakage.

	Further study of early leakage by Chia and Goldberg noted the striking rate of 44 percent early leaks in eyes having extracapsular cataract surgery compared to 24 percent leakage in those undergoing phacoemulsification.101  Other differences in leakage were reported for fornix-based flaps (eight percent leakage) versus limbus based (less than one percent), by Tezel and colleagues16 and for two-site cataract/trabeculectomy surgery (9 percent) compared to one-site 

surgery (4 percent), by El Sayyad and colleagues.86  It is safe to say that reporting criteria for such leakage must have varied dramatically (and in ways that are not apparent from the reports themselves) to lead to such large differences in absolute rates. 

	Choroidal effusion is a finding associated with lower eye pressure in the postoperative period, and a complication that is notoriously under-reported unless examinations are specifically targeted to find it. In the 89 reports evaluated, choroidal effusion is noted in 47, with up to 15 percent of eyes having this complication. Among eyes that underwent combined cataract/trabeculectomy surgery, there were only a few associations with higher effusion rates. Fornix-based conjunctival flaps were reported to be associated with choroidal effusion in eight percent of eyes compared to two percent of eyes having limbus-based flaps.14  Reports by Kosmin21 and by Lyle18 reached contradictory conclusions regarding the association of effusions and incision size in combined cataract trabeculectomy surgery.  The former reported effusions in 15 percent of those with smaller incisions compared to three percent of those with larger incisions.  The latter reported effusions in 12 percent of those with larger incisions compared to three percent of those with smaller incisions.

	Early endophthalmitis was essentially unreported, and since this complication is highly evident and typically a dramatic event, it is likely that few reports actually had cases of this problem in their populations studied.  However, the likely rate of one infection per 1,000 operations would never have been detected in studies with the small sample sizes evaluated here.113

	Epithelial defects are a problem largely engendered by the use of anti-fibrosis treatment with 5-fluorouracil.  In eyes undergoing combined phacoemulsification and cataract extraction, O'Grady and colleagues reported 10 eyes with epithelial defects in the 5-fluorouracil treated eyes versus zero eyes in the control group.90  Wong and colleagues 89 reported an incidence of 67 percent in eyes receiving 5-fluorouracil versus 35 percent in the controls; whereas Chia101 noted a rate of 56 percent among extracapsular cataract procedures combined with trabeculectomy compared to 32 percent in phacoemulsification trabeculectomy, both groups being treated with 5-fluorouracil.  None of the studies using mitomycin-C for anti-fibrosis reported any epithelial effects-consistent with the lack of effect of this drug on epithelial cells.

	A severe (fibrinous) inflammatory reaction occurred in one percent or fewer of eyes in most reports, though lack of comment may not necessarily mean that no such reactions occurred. However, some investigations reported high rates of fibrinous reactions, including a study by Chia101 using 5-fluorouracil, a study by Cohen79 using mitomycin-C, and a study by Borggrefe95 not using anti-fibrosis agents.  However, the rates of severe inflammation in these reports varied from 20 percent to 60 percent.  By contrast, Krupin and colleagues found no examples of fibrinous reactions among 68 cases of extracapsular surgery.51  The definition of fibrinous reaction may have varied dramatically among these studies and may explain the inconsistent conclusions.

	Hyphema or bleeding into the anterior chamber soon after surgery can vary from barely detectable to a large amount of blood. Again, for this early complication, rates reported vary from less than 10 percent of eyes undergoing trabeculectomy alone or combined with cataract surgery in the largest series, to more than 50 percent of eyes in one report. Reports indicated possibly higher rates with two-site combined surgery100, higher doses of mitomycin-C72, phacoemulsification compared to nuclear expression101, extracapsular surgery105, and higher in large compared to small incision cataract/ trabeculectomy incisions.18

	Hypotony can lead to secondary vision loss on a short-term or permanent basis. The typical rate among many studies reviewed for low pressure (usually considered to be 5 mm Hg or less) is 10 to15 percent. Blondeau and Phelps reported a higher rate of hypotony for thermosclerostomy versus trabeculectomy glaucoma surgery (20 percent versus 10 percent).74   Borggrefe and others found hypotony in 16 percent of eyes undergoing a one-site combined procedure compared to 4 percent with a two-site cataract/trabeculectomy.95  Lemon and others83 found a higher rate of hypotony with limbus versus fornix flaps (30 percent versus eight percent) and Wishart and Austin105 reported hypotony in 36 percent of eyes after nuclear expression versus 15 percent of eyes after phacoemulsification.

	Likewise, suprachoroidal hemorrhage is a vision threatening condition related to hypotony and wound leaks. This complication was highest in a series by Sanders and others72 using mitomycin-C (six percent), and lowest in combined cataract/trabeculectomy both with an anti-fibrosis agent (one percent)77 or without an anti-fibrosis agent (one percent).16, 103   This would be expected if combined procedures give fewer low pressures due to more complete healing of the surgery.

	The final early complication documented was vitreous hemorrhage, seen infrequently, and at its maximum (six percent) in eyes undergoing trabeculectomy with mitomycin-C treatment.72  In combined procedures using mitomycin-C a representative rate would seem to be that in a study by Tezel's group, who reported eight cases of vitreous hemorrhage in 397 eyes (two percent).103  This complication is unlikely to have escaped detection, as it is a cause of serious vision decrease and is readily visible.

Late Complications					

	Late complications included the Tenon cyst, a solid elevation of the bleb usually associated with higher than desired eye pressure. This was not often noted in most studies, although whether due to lack of occurrence or failure to report cannot be determined. The highest rate was three percent in one trabeculectomy series by Cheung and colleagues.62

	Late bleb leakage was also infrequently reported.  Of 300 eyes undergoing surgery in a controlled trial in India, Robin and colleagues, reported one leakage during 12 months followup.70  Shingleton14 and Caprioli 23 respectively had less than one percent, and zero of 80 cases, respectively, of this problem to report. The problem of late wound leakage (any leakage related to the wound) is easily confused with late bleb leakage, (leaks confined to the surface of the bleb).  It is not clear that each study differentiated these in this way. In one of the few long-term studies, Lewis and Phelps found that 13 percent of eyes after glaucoma surgery alone developed a wound leak (almost surely this is identical to a bleb leak).78  In combined surgery, leakage was less common (three percent at 1 year after combined surgery without anti-fibrosis, as reported by Anand and colleagues99), and less than one percent of 612 eyes in combined surgery with mitomycin-C as reported in two studies by Tezel's group.16, 103 

	Cystoid macular edema was noted in fewer than two percent of cases in most studies, and was remarkable for the lack of differences related to technique variations. This is possibly due to the lack of performance of fluorescein angiography needed to make any definitive statement about the presence of this complication.

	Late endophthalmitis was noted in only 3 eyes of all the reports, Carlson80, Sanders72, and Yang.27  Since it occurs at a rate of fewer than one per 1,000 per year of followup, each series would have only trivial power to detect this problem.113

	Corneal graft failure was not noted in any study, surely due to the lack of significant numbers of cases of those who had penetrating keratoplasty with secondary glaucoma in these reports.

	Hypotony maculopathy was not reported in any of the series that did not use an anti- fibrosis agent. Hence, it can be speculated that it is either a direct result of the drugs themselves or a result of the low pressure that is generated by their use.  Robin70 found three percent of trabeculectomies with mitomycin-C treatment had hypotony maculopathy, while none of those without mitomycin-C had it. Budenz found one of 71 eyes with this complication, and it did not occur in the group not receiving anti-fibrosis agents.84  Tezel's group16,103 and El- Sayyad and colleagues86 detected it in eight percent and two percent, respectively, of their combined cataract/trabeculectomy series, all of whom had received mitomycin-C.

	Posterior capsule opacity leads to decreased vision, but there is difficulty in determining whether authors were reporting simply its initial presence or an opacity sufficient to obscure vision or to lead to YAG laser capsulotomy to relieve the problem. Furthermore, the progressive opacity should be evaluated as an incident rate per unit time, and many of our studies did not report the length of followup or if they did, the timing of the capsule opacity was not given. Within the first 2 years after cataract surgery in glaucoma subjects, between 12 percent27 to 50 percent101, of eyes were reported to develop capsule opacity.  The rate did not appear associated with any particular method of surgery, nor was it related to use of anti-fibrosis therapy. Two large cohort studies by Tezel and colleagues16,103  of phacoemulsification combined surgery had a rate of 25 percent, while a large series of extracapsular surgery42, had a similar rate, 30 percent. Clearly, longer followup would be likely to increase the proportion affected and some method of standardizing the reporting of this problem would be helpful.	

	Shin, Kim, Ren and colleagues87 evaluated the incidence of posterior capsular opacification in eyes without previous glaucoma surgery receiving mitomycin-C or placebo at the time of combined phacoemulsification and trabeculectomy.  Using life table analysis they found that YAG capsulotomy was performed less frequently in the eyes that received mitomycin-C (p = 0.004).  For instance, the proportion of eyes receiving capsulotomy by 4 years after surgery was approximately 60 percent in the placebo group and 40 percent of the mitomycin-C group.