Effects of Combined Cataract Surgery on Outcomes of Descemet’s Membrane Endothelial Keratoplasty: A Systematic Review and Meta-Analysis

Authors: Tey KY, Tan SY, Ting DSJ, Mehta JS, Ang M.

Geographical coverage: Netherlands, Germany, France, Italy, Spain, United Kingdom, United States, Canada, Egypt, Nepal, and a multicentre study spanning 23 countries

Sector: Cataract surgery

Sub-sector: Treatment comparison

Equity focus: Not reported

Study population: Patients with cataract

Review type: Effectiveness review

Quantitative synthesis method: Meta-analysis

Qualitative synthesis method: Not applicable

Background:

Cataract surgery is the most commonly performed elective procedure globally, with over 10 million operations each year. Corneal endothelial diseases, such as Fuchs’ endothelial dystrophy (FECD), continue to be major causes of vision loss and are leading indications for corneal transplantation. Descemet’s membrane endothelial keratoplasty (DMEK) is now the preferred treatment for corneal endothelial dysfunction due to its excellent visual outcomes and low rejection rates. Performing cataract extraction concurrently with DMEK (often termed “triple DMEK”) offers benefits such as cost-effectiveness and improved intraoperative clarity, but concerns remain about increased risks of complications (for example, graft detachment). Consequently, there is still no consensus on the optimal surgical approach for patients with coexisting cataract and corneal endothelial disease.

Objective:

To appraise and compare the published evidence on surgical outcomes of DMEK alone versus combined cataract surgery with DMEK (“triple DMEK”), in order to inform future clinical practice in managing patients with coexisting corneal endothelial disease and cataract.

Main findings:

This review included 36 studies, covering a total of 11,401 eyes. The studies were conducted in a range of countries (notably the Netherlands, Germany, the United States of America, Canada, Egypt, France, Italy, Nepal, Spain, the United Kingdom, and a large multicentre study spanning 23 countries). The methodological quality of these studies varied.

There was no significant difference in graft re-bubbling (repeat air injection) rates between combined surgery and DMEK alone. Approximately 27.4% of eyes required re-bubbling after triple DMEK, compared to about 22.4% after DMEK alone (risk difference ≈ –0.06; 95% confidence interval (CI): –0.13 to 0.00; I2 = 73%; p = 0.07), indicating a statistically non-significant trend towards slightly more re-bubbling with the combined procedure.

Limited data were available for a direct comparison of graft detachment rates between the two approaches. In non-comparative DMEK studies (DMEK without cataract surgery), the rate of graft detachment (partial or complete) was about 8.3% of eyes. This appears similar to the graft detachment incidence reported in triple DMEK cases (also roughly 8%). However, due to the lack of studies directly comparing the two, it remains uncertain whether the combined procedure significantly affects the risk of graft detachment.

Patients who underwent triple DMEK achieved slightly better early visual acuity. At one month postoperatively, the triple DMEK group had better best-corrected visual acuity (BCVA) by an average of 0.10 logMAR (approximately one line on an eye chart; 95% CI: 0.07 to 0.13; p < 0.001) compared to the DMEK-only group. This early advantage diminished by 3–6 months post-surgery: by that time, the difference was around 0.07 logMAR (95% CI: –0.01 to 0.15; p = 0.08), which is not statistically significant. In practical terms, both groups achieved comparable vision by three to six months after surgery.

The loss of corneal endothelial cells after surgery was similar whether or not cataract surgery was combined with DMEK. At three months, the difference in endothelial cell loss between the DMEK-only and triple DMEK groups was about –3.24% (p = 0.29), and at six months it was +2.93% (p = 0.40). These small differences were not statistically significant, suggesting that adding cataract surgery did not notably impact endothelial cell survival in the early postoperative period.

The incidence of primary graft failure (failure of the corneal graft to function, requiring re-transplant) did not differ significantly between combined surgery and DMEK alone. The risk difference was roughly 0.01 (95% CI: –0.02 to 0.05; p = 0.44), indicating no meaningful difference in graft failure rates.

Other postoperative complications were comparable between the two surgical approaches. The rates of cystoid macular oedema (retinal swelling) and posterior capsular rupture (a complication during cataract removal) were similar in both groups (p = 0.70 and p = 0.15, respectively). It is worth noting that among patients who underwent DMEK alone (leaving the natural lens in place), about 13.5% experienced significant cataract progression in the months following surgery, particularly in older patients. This highlights a potential advantage of performing the combined procedure (triple DMEK) in suitable patients, as it addresses the cataract at the same time and may prevent the need for a second surgery later on.

Methodology:

The literature search was conducted in PubMed, Web of Science, Cochrane Library, and ClinicalTrials.gov. The reviewers sought both randomised and non-randomised studies (including large prospective and retrospective case series) that reported surgical outcomes of DMEK for corneal endothelial dysfunction, with or without concurrent cataract surgery. No restrictions were placed on language, publication date, or publication status. The reference lists of all included studies, as well as relevant review articles, were scanned for any additional publications.

Study selection and quality assessment were performed carefully. Two reviewers independently screened the search results to identify eligible studies. They also independently assessed the risk of bias of the included studies: for any randomised controlled trials (RCTs), criteria from the Cochrane Handbook for Systematic Reviews of Interventions (Chapter 8) were used, and for non-randomised studies, the Risk of Bias in Non-Randomised Studies of Interventions (ROBINS-I) tool was applied. Any discrepancies between the reviewers were resolved through discussion or by consulting a third reviewer.

Data from the included studies were synthesised using a random-effects model meta-analysis, which accounts for variability between studies. Heterogeneity between study results was evaluated using the I2 statistic (which indicated substantial heterogeneity for some outcomes, such as re-bubbling). A funnel plot was used to assess potential publication bias. Additionally, the overall certainty of the evidence for key outcomes was assessed using the GRADE framework (Grading of Recommendations Assessment, Development and Evaluation), although this assessment was carried out by a single reviewer.

Applicability/External Validity

The conclusions of this review are limited by the nature of the available evidence. Notably, there were no direct RCTs comparing DMEK alone versus combined cataract plus DMEK surgery. Most included studies were observational or case series, and their quality varied, with significant heterogeneity across reported outcomes. As a result, it is difficult to make definitive, generalisable recommendations based on the current evidence. The authors highlight a clear gap in the literature and emphasise the need for well-designed, adequately powered RCTs to evaluate the long-term outcomes of combined (triple) versus separate (staged) DMEK procedures. Such future studies would help determine the optimal approach for managing patients with both corneal endothelial disease and cataract, and would strengthen the external validity of the findings.

Geographical Focus

No geographical limitations were applied to the search strategy. The studies included in this review were drawn from a wide range of regions. A large proportion of the data comes from Europe (particularly the Netherlands and Germany, with additional studies from France, Italy, Spain, and the United Kingdom) and North America (United States and Canada). There were also contributions from Africa (Egypt) and Asia (Nepal), as well as one multicentre study spanning 23 countries. This broad geographic representation suggests the findings are relevant across diverse healthcare settings, although differences in surgical practice or patient populations in regions not covered by the included studies are not accounted for in the review.

Summary of Quality Assessment

The review comprehensively searched multiple databases and used robust selection and appraisal methods. However, most included studies were observational and varied in quality, and some methodological details were lacking. As a result, confidence in the review’s conclusions about combined cataract surgery and DMEK versus DMEK alone is low, highlighting the need for higher-quality future research.