Summary

Overview

Cataract and glaucoma are both common conditions and are often present in the same patient. Cataract surgery is the most commonly performed surgical procedure on Medicare beneficiaries. In 1998, approximately 1.4 million cataract surgeries were performed on Medicare beneficiaries. Primary open-angle glaucoma affects at least 2.5 million individuals in the United States, predominantly adults over 50 years of age. The total direct cost expenditures for glaucoma therapy have been estimated at $1.56 billion per year.

Although guidelines exist for the indications for cataract surgery in the otherwise healthy eye and for glaucoma surgery in eyes with glaucoma, there is controversy concerning the indications for surgery when both cataract and glaucoma are present. In addition, there is no clear consensus about the appropriate timing of the surgery for either condition, or about the best surgical technique. Furthermore, there is no agreement concerning the optimal management of these disorders when coexistent. Therefore, the Agency for Healthcare Research and Quality (AHRQ), (formerly the Agency for Health Care Policy and Research), awarded a contract to the Johns Hopkins University Evidence-based Practice Center to prepare an evidence report on the topic. This evidence report was undertaken to identify the most important questions pertinent to surgical treatment of  coexisting cataract and glaucoma, to assess the quality and content of the evidence on surgical treatment of coexistent cataract and glaucoma, and to inform clinical practitioners and identify areas where future research is needed.

Reporting the Evidence

The target population addressed in this evidence report is adult patients with coexisting cataract and glaucoma. Both open- and closed-angle glaucoma were considered. The target audience for the report is health care professionals involved in the care of adult patients with coexisting cataract and glaucoma.

The following questions were addressed in the evidence report:

•	What are the risks and benefits of staged versus combined procedures for coexisting cataract and glaucoma? 

•	What is the effect of cataract surgery on short- and long-term intraocular pressure (IOP) control in open-angle glaucoma patients? 

•	What is the effect of glaucoma surgery (i.e., filtration surgery) on the development and progression of cataract? 

•	What are the risks and benefits of antifibrosis agents in the surgical treatment of coexisting cataract and glaucoma? 

•	What are the risks and benefits of trabeculectomy versus endoscopic laser versus deep sclerectomy/viscocanulostomy in patients with coexisting cataract and glaucoma? 

•	What are the risks and benefits of single-site versus two-site operations for coexisting cataract and glaucoma? 

•	What are the risks and benefits of nuclear expression or phacoemulsification in patients with coexisting cataract and glaucoma?

The interventions evaluated included two commonly used methods for cataract extraction: nuclear expression and phacoemulsification. Several methods used for the surgical management of glaucoma were studied, including laser treatment, filtration surgery, and the newer techniques of endoscopic cyclophotocoagulation and the so-called nonpenetrating procedures. The use of the antifibrosis agents 5-fluorouracil and mitomycin C was also evaluated. The various ways in which cataract and glaucoma surgery can be performed either simultaneously or sequentially were studied.

The primary outcome assessed for the questions involving glaucoma surgery was IOP, both in the immediate postoperative period and long term. The articles reviewed generally lacked useful data on optic nerve appearance and visual fields, thereby precluding a meaningful review of those outcomes. Likewise, the lack of information concerning complications limited the ability to address the risk aspects of each question. For the question concerning the development of cataract after glaucoma surgery, both the observation of a cataract and the performance of cataract surgery were assessed outcomes.

Methodology

The literature searches were conducted using two electronic databases, PubMed and CENTRAL, the Cochrane Collaboration’s database. The textwords and medical subject heading (MeSH) terms we used included (“cataract” and “glaucoma”) and (“surgery” or “filtering surgery” or “cataract extraction” or “sclerostomy” or “trabeculectomy” or “phacoemulsification”). To retrieve the appropriate types of studies, we included variants of randomized controlled trials in the search as well as “case report” and “case series.” We limited the search to publications in English. Citations spanned the period from 1980 to April 2000. The electronic searches were augmented by a hand search of primary journals.

The abstracts of all identified citations were independently reviewed by two members of the study team to determine if they met eligibility criteria. When reviewing abstracts, the following criteria were used to exclude articles from further consideration: lack of adults in the study population, lack of original data, failure to include human data, failure to address open-angle glaucoma or primary angle closure glaucoma, neither a controlled trial nor a case series greater than or equal to 100 eyes, addressing only intracapsular cataract surgery, and addressing only full-thickness procedures.  Meeting abstracts and texts not in English were also excluded. Disagreements between reviewers about the eligibility of  a citation were adjudicated at a meeting of the entire study team. We reviewed the full text of the article for a 5-percent random sample of rejected abstracts. None of these articles was deemed eligible for inclusion in the full article review.

Two forms were developed and used to review eligible citations. The quality assessment form contained questions grouped into the following categories:

•	Representativeness of study population—how completely the authors described the study subjects. 

•	Bias and confounding, including completeness of randomization and masking. 

•	Description of therapy—completeness of the description of the study protocol and other treatments, if applicable. Outcomes and followup, including explicit description of the outcomes reported (e.g., assessment of IOP, cataract assessment) and length of followup. 

•	Statistical quality and interpretation.

Quality scores for each controlled trial and cohort study were tabulated.

The article content assessment form was developed through an iterative process. The study team discussed which outcomes should be included on the form. Following these discussions, selected relevant articles were reviewed to create a standardized abstraction of reported outcomes in a manner that was applicable across the range of studies. Finally, the form was pilot tested on a sample of articles and revised as necessary. Instructions for the use of the form were developed by consensus for the purposes of consistency.

Each article identified by the search process and determined to meet eligibility criteria through the abstract process was reviewed by two reviewers. At least one of the reviewers was trained in research methodology and at least one was trained in ophthalmology or internal medicine.

Data from the article review process were entered into a relational database. For each study question, one member of the analysis team summarized the available data and reached a conclusion about the answer to the question. The entire study team assigned an evidence grade to the conclusions reached about each study question.

Findings

Of 919 unique, potentially relevant citations, 131 articles were eligible for full article review. After 21 were excluded, 110 articles remained for data extraction. Study quality scores were calculated for controlled trials and cohort studies, comprising 81 articles. The mean overall study quality score was 53 percent.

The findings are as follows:

Strongly Supported by the Literature

●	Glaucoma surgery was associated with an increased risk of postoperative cataract. 

●	A glaucoma procedure added to cataract surgery lowers IOP more than cataract surgery alone.

Moderately Supported by the Literature

●	Limbus- and fornix-based conjunctival incisions provided the same degree of  long-term IOP lowering in combined surgery. 

●	In combined surgery using phacoemulsification, the size of the cataract  incision did not affect long-term IOP control. 

●	5-fluorouracil was not beneficial in further lowering IOP when used with combined procedures. 

●	Mitomycin C was efficacious in producing lower long-term IOPs when used with combined procedures.

Weakly Supported by the Literature

●	Combined procedures resulted in lower IOP at 24 hours than cataract extraction  alone. 

●	Extracapsular cataract extraction (ECCE) alone appears to increase IOP at 24 hours. 

●	In the long term, cataract surgery alone lowered IOP by 2 to 4 mm Hg, combined cataract and glaucoma surgery lowered IOP by 6 to 8 mm Hg, and the performance of a glaucoma procedure alone provided even greater long-term IOP lowering  than combined cataract and glaucoma surgery. 

●	Combined surgery in which the incisions for the cataract extraction and  glaucoma procedure are separate provided slightly lower long-term IOP than a one-site approach. 

●	Combined surgery in which phacoemulsification is used provided slightly lower long-term IOP than nuclear expression. 

●	The same complications occurred with combined surgery as occur with cataract  and glaucoma surgery performed separately. 

●	5-fluorouracil use was associated with epithelial defects. 

●	Hypotony was more likely after the use of antifibrosis agents than after surgery performed without antifibrosis agents.

Future Research

The literature addressing management of coexistent cataract and glaucoma has important limitations that future research should consider and address. First, those limitations pertaining to the entire literature are described, and then those that are specific to individual questions are described.

In terms of the management of glaucoma, because the extant literature concentrates on IOP, this review was limited to the effect of surgery on IOP. Future studies should assess the effect of surgery on the appearance of the optic nerve, visual field, and quality of life. Because of the chronic and slowly progressive nature of glaucoma, these parameters need to be evaluated in 

long-term (5 years or more) studies.

In terms of cataract, future studies should pay more attention to the quantification of cataract and its effect on vision. The existing literature is generally lacking in any objective description of the ocular lens, whether clear or cataractous. Quantifying lens opacity and assessing its effect on 

vision and vision-related quality of life should be a priority in future studies. Standardized grading systems for cataract (already in use) should be employed.

Although the literature represented populations in North America, Europe, and Asia, few of the reports included significant numbers of black Americans. This population has a high prevalence of glaucoma and may respond differently to glaucoma surgery. Future researchers should strive to include more black Americans in their studies.

Assessment of the evidence was limited by the quality of the literature. In several of the study quality categories, particularly bias and confounding, there was tremendous room for improvement. A lack of comparability of study groups and an absence of masking of observers greatly compromised the validity of many studies. In future studies, it would be valuable to strive for comparability of study groups and statistical adjustment for baseline differences, as well as more objective measures for assessing outcomes.

The following specific questions are areas for future research, both because of their importance and the fact that questions remain unresolved by the extant literature:

•	Does trabeculectomy alone lower IOP more than phacoemulsification plus trabeculectomy?

•	Does phacoemulsification harm functioning filtering blebs? 

•	Does phacoemulsification reliably result in lower IOP on the first day after surgery? If so, then it might not be necessary to perform combined surgery. 

•	Does a two-stage procedure provide lower IOP than a combined procedure?   What is the role of mitomycin C in combined procedures and how should it be  administered? 

•	Is the finding of decreased posterior capsular opacification with the use of  mitomycin C reproducible? 

•	Can better glaucoma procedures be developed to be used in conjunction with cataract surgery? 

•	What are the risk factors for cataract development and progression following glaucoma surgery?