The Use of Prostaglandin Analogues and Cystoid Macular Edema after Uneventful Cataract Surgery: A Systematic Review and Meta-Analysis

Authors: Özyol E, Özyol P, Günel-Karadeniz P.

Geographical coverage: USA, Canada, Japan, South Korea, Iran, and UK

Sector: Cataract surgery

Sub-sector: Cystoid macular oedema

Equity focus: Not reported

Study population: Patients with cataract

Review type: Effectiveness review

Quantitative synthesis method: Meta-analysis

Qualitative synthesis method: Not applicable

Background:

Cystoid macular oedema (CME) is one of the most common complications following uneventful cataract surgery and a significant cause of reduced postoperative visual acuity. The reported incidence of CME varies widely due to differences in diagnostic techniques, but it typically occurs around 4 to 6 weeks after surgery. Several risk factors for CME have been identified, including diabetes, uveitis, retinal disorders, surgical trauma, and elevated intraocular pressure. The use of prostaglandin analogues (PGAs), which are commonly used in glaucoma treatment to lower intraocular pressure, has also been suggested as a potential risk factor. However, studies have shown conflicting results: some link PGAs to the development of CME, while others find no association. Clarifying this relationship is crucial for postoperative management, given the widespread use of PGAs and the frequency of cataract surgeries.

Objective:

To evaluate whether the perioperative use of PGAs is associated with an increased rate of developing clinical or subclinical CME after uneventful cataract surgery.

Main Findings:

Nine studies were included in this meta-analysis. The studies varied in design, comprising three randomised controlled trials (RCTs), one prospective cohort study, one prospective interventional case series, three retrospective cohort studies, and one retrospective case–control study. Three of the nine studies were conducted in the USA, two in the UK, and one each in Canada, Japan, South Korea, and Iran.

The meta-analysis found that continuing PGAs during the perioperative period was not associated with an increased risk of developing subclinical CME compared to discontinuing PGAs (odds ratio [OR] 1.32, 95% confidence interval [CI] 0.49–3.51; p = 0.582). The overall incidence of CME in patients who continued PGAs was 34% (95% CI 0.17–0.52; p < 0.001), compared to 7% (95% CI 0.02–0.13; p = 0.006) in those who discontinued PGAs. In a subgroup analysis limited to clinically significant CME (excluding lower-quality studies), the incidence among continued PGA users was 6% (95% CI 0.01–0.11; p = 0.010).

When comparing PGA users to patients using other (non-PGA) glaucoma medications, continued PGA use did not significantly increase the risk of CME (OR 2.29, 95% CI 0.84–6.23; p = 0.103). Overall, the findings suggest that discontinuing PGAs around the time of surgery in eyes without known risk factors for CME does not have a clinically significant effect on reducing the risk of postoperative CME.

Methodology:

The literature search was conducted in PubMed, Scopus, and ScienceDirect up to June 2022, to identify English-language studies investigating the relationship between PGA use and the development of CME after cataract surgery. The reference lists of included studies were also scanned for any additional relevant publications. Two reviewers independently screened the search results, selected the studies, extracted data, and assessed the risk of bias in the included studies using the Newcastle-Ottawa Scale. Any discrepancies between reviewers were resolved through discussion. The data were combined using a random-effects model meta-analysis, and heterogeneity across studies was assessed using the I² statistic.

Applicability/External Validity:

The review did not explicitly discuss the applicability or external validity of its findings. However, it noted that variations in how CME was defined, the diagnostic methods used, and the length of follow-up across studies may affect how generalisable the results are to different clinical settings. The authors highlighted the limited number of RCTs available and emphasised the need for further well-designed prospective RCTs to clarify the relationship between PGA use and CME. Such studies would help in developing practical guidelines for cataract surgeons regarding the management of PGAs in the perioperative period.

Geographical Focus:

No geographical limits were applied to the search. The included studies were conducted in North America (USA and Canada), Asia (Japan, South Korea, and Iran), and Europe (UK), indicating a broad international representation.

Summary of Quality Assessment:

Overall, there is medium confidence in the conclusions of this review. The literature search was comprehensive and the inclusion/exclusion criteria were clearly defined. Two reviewers worked independently to screen studies, extract data, and assess risk of bias, using established tools and resolving disagreements by discussion. The characteristics of the included studies were well documented, and the meta-analyses were appropriately performed with consideration of heterogeneity. On the other hand, the search was limited to English-language publications, which may introduce language bias, and the review did not provide a list of excluded studies. These limitations should be kept in mind when interpreting the results and conclusions.