Chapter 4: Conclusions

Principal Findings

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.

•	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 anti-fibrosis agents than after surgery performed without antifibrosis agents.

Limitations of the Literature

	Although the literature on the management of coexistent cataract and glaucoma allowed us to draw the above conclusions, it had important limitations. 

	First, in terms of the management of glaucoma, we were forced to limit our review to the effect of surgery upon intraocular pressure (IOP).  It is well accepted that the level of IOP is not the disease, but simply an important risk factor.  The effect of surgery upon the clinical course of glaucoma would be more appropriately determined by evaluating its long-term effect upon the appearance of the optic nerve, visual field, and quality of life.  Very few of the articles that we reviewed reported data on the optic nerve or visual field.

	The reasons for this deficiency in the literature are several.  First, glaucoma is generally a slowly progressive disease, so to detect worsening or stabilization of the optic nerve or visual field would take a study of at least 3, and more likely 5 to 10 years, in duration.  Most of the articles reviewed had much shorter durations of followup.  Secondly, because of the variability of visual field testing, it is a daunting task, even over a several year period, to definitively document deterioration of the visual field.  Likewise, our ability to detect changes in the appearance of the optic nerve in a reproducible fashion is limited.  Finally, the presence of coexisting cataract and glaucoma presents unique problems in monitoring the optic nerve and visual field.  Specifically, the presence of a cataract can make preoperative assessment of the optic nerve difficult or impossible, because the examiner, or examining device, cannot see the optic nerve through an opaque cataract.  Furthermore, cataract and its removal affect the visual field, and it can be difficult to separate out whether changes in the visual field are due to cataract or glaucoma.  In an eye with increasing cataract after glaucoma surgery, it is particularly difficult to determine whether worsening in the visual field is due to glaucoma or cataract.

	In terms of cataract, the literature was generally deficient in any objective description of the ocular lens, whether clear or cataractous.  Many studies simply state that the eyes undergoing surgery had cataracts, without providing an assessment of the severity of the cataract.  Particularly in the studies commenting on cataract after glaucoma surgery, we usually could not tell if cataract was simply an observed lens opacity, or visually significant.  No standardized grading of cataract was reported.

	Assessment of the literature was limited by its quality.  Although the overall study quality score for the articles reviewed was higher (53 percent) than in some other evidence reports, such as the Report on Anesthesia Management During Cataract Surgery (overall mean study quality score of 44 percent), in some categories of study quality, particularly bias and confounding the score was very low (mean of 30 percent).6  In many studies, a lack of comparability of study groups and an absence of masking of observers greatly compromised their validity.

	In addition to these general comments concerning deficiencies in the literature we uncovered gaps in the literature concerning the specific questions that were asked.	

Long-term Control of IOP 

	There were only two randomized controlled trials comparing phacoemulsification to phacoemulsification plus trabeculectomy. One of those trials enrolled only 10 patients per group.  The other trial used an unusual approach to performing the trabeculectomy (a no-stitch technique).  While the results of these two studies agreed with the expectation that combined procedures produce a larger decrease in IOP than cataract extraction alone, the evidence is weak.

  	The evidence is weak that phacoemulsification plus trabeculectomy results in less IOP lowering than trabeculectomy alone.  No randomized trials addressed this question.  This is an important issue when deciding whether or not to perform a combined procedure in a glaucoma patient with uncontrolled glaucoma.  

	While extracapsular cataract extraction (ECCE) and phacoemulsification both appear to lower IOP, the evidence that phacoemulsification lowers IOP by a greater amount was only found when comparing the results of case series and non-randomized controlled trials.  If indeed phacoemulsification reduces IOP more than ECCE, then clinicians might alter the surgical approach in individuals with ocular hypertension or glaucoma.  A randomized controlled trial would help to address this question.

	The evidence that phacoemulsification does not harm functioning filtering blebs is quite limited, with only two articles looking at this question.  Further research in this area would be of great importance to clinicians.  If the IOP lowering effect is greater performing trabeculectomy alone than in a combined procedure, and if the bleb is not affected by later clear cornea phacoemulsification, then this would argue for sequential surgery in most patients with cataract and glaucoma. 

Short-term IOP Control

	While early studies found large increases in IOP immediately after ECCE in patients with glaucoma, later research with phacoemulsification found mean decreases in IOP on the first postoperative visit.  Data are limited, however, and larger series are needed to confirm that immediate IOP spikes are not common using phacoemulsification techniques.  If immediate IOP spikes are not common after phacoemulsification alone in glaucoma eyes, then it might not be  necessary to perform combined surgery as often.

	The data supporting different regimens to control postoperative IOP spikes in individuals with glaucoma are limited.  More research on the best regimen for preventing immediate postoperative IOP spikes would be valuable to clinicians.

One- versus Two-site Surgery

	Several studies have been performed, both with and without anti-fibrosis agents.  The consensus is that two-site surgery may result in slightly lower IOP in aggregate than single-site surgery.  However, none of the studies included African-Americans, a group with a high prevalence of glaucoma and in whom responses to surgery may differ from Caucasians. 

Simultaneous versus Sequential Cataract and Glaucoma Surgery

	The number of studies (three) addressing this question was small, and no randomized trial has been performed.  Even if the ultimate effect on IOP is better with the two-staged procedure, quality of life concerns about the disadvantages of deferring visual improvement and the necessity of two operations in the staged strategy need to be addressed. 

Mitomycin-C in Combined Procedures

	Only one study looked at the role of mitomycin-C in African-American patients.  No consensus exists in the literature regarding the optimal dose and duration of mitomycin-C use.  Furthermore, no studies have attempted to confirm or refute the interesting finding of decreased posterior capsular opacification in eyes treated with mitomycin-C.  The finding in one study of decreased posterior capsular opacification is an intriguing finding that merits further investigation.

Trabeculectomy Combined with Cataract Surgery Compared with Other Types of Glaucoma Surgery Combined with Cataract Surgery

	The literature is scant on the use of endoscopic laser treatment and non-penetrating glaucoma surgery in conjunction with cataract surgery.  Before other procedures are adopted, more and higher quality studies will need to be done.

Implications

	The findings of this report can serve both to give support to certain strategies now being used to manage coexistent cataract and glaucoma and to highlight areas in which physician behavior is not informed by adequate information.  It can serve as an impetus to future research on the important unresolved questions and point toward better ways of designing and reporting the results of future studies.  Chapter 5 contains a more detailed discussion of future research implications.