Comment on of “Effect of ginkgo biloba extracts in the prevention of posterior capsule opacification after cataract surgery: A randomized clinical trial”

Dear Editor, We read with great interest Amiri et al.’s article, which evaluated Ginkgo biloba extract (GbE) in the prevention of posterior capsule opacification (PCO) after cataract surgery using a randomized clinical trial design.[1] The study tackles a clinically significant issue, as PCO is still a major cause of late vision deterioration after cataract surgery, frequently needing an Nd:YAG capsulotomy, which carries procedural risks and healthcare expenditures.[2,3] While the experiment provides valuable insights, some methodological and interpretation issues require additional vigilance and consideration. The study was carefully constructed as a double-blind, placebo-controlled randomized experiment with a 36-month follow-up period. The adoption of a single intraocular lens model and a consistent surgical method reduced procedural variability, which improved internal validity. Furthermore, the authors found a clinically significant reduction in Nd:YAG capsulotomy rates in the GbE group (6.1%) compared to the placebo (20.4%), indicating possible prophylactic benefit.[1] Although the authors provided proper randomization and double blinding, the allocation concealment method (“numbered containers”) could have been discussed further to determine whether sequentially numbered, opaque, sealed envelopes or equivalent rigorous methods were utilized. Transparency about code-breaking processes and intermediate analyses would boost confidence in blinding integrity.[4] The sample size calculation assumed a 20% difference in visual acuity outcomes between groups; however, it is unclear if this estimate was based on previously collected GbE data or extrapolated from unrelated interventions. This raises questions about whether the study was appropriately powered to detect meaningful changes in PCO severity levels, not simply Nd:YAG frequency. PCO was rated using slit-lamp biomicroscopy with semi-quantitative scoring (0–4), but the authors concede that manual grading is inherently subjective. Objective, proven technologies, such as the evaluation of posterior capsular opacification or the AQUA system, could have produced more reproducible results and simplified inter-study comparisons.[5] Furthermore, the study fails to reveal inter-rater reliability for PCO grading. The exclusion of patients with diabetes, hypertension, or ocular comorbidities enhances internal control while reducing external validity. Many real-world cataract patients have these disorders, all of which are known risk factors for PCO.[3] Furthermore, the authors state that dietary patterns were “not monitored,” which could skew the results, given that antioxidant intake may increase PCO risk. While statistically significant differences in pearl and fibrotic PCO scores were observed at 12 and 36 months, respectively, the therapeutic relevance of these score alterations on functional vision is unclear. The reported mean LogMAR differences, while statistically significant (P = 0.005), may not meet the criteria for clinically noticeable change. The authors state “no adverse events,” but mainly gastrointestinal distress and skin responses were seen. Given GbE’s known interactions with anticoagulants and the risk of bleeding, a more extensive safety surveillance plan (including coagulation profiles) would support the safety conclusions.[6] The authors’ conclusion is that GbE “may provide marginal prevention of PCO formation.” While the Nd:YAG reduction is remarkable, the term “marginal” refers to the minor PCO score difference and effect size recorded. More multicenter trials in varied populations are needed before GbE may be advised as an adjuvant in routine cataract surgery. The work is a significant first step toward investigating nutraceutical methods to PCO prophylaxis. However, limitations in outcome assessment methodologies, a small patient group, and safety surveillance reduce the findings’ generalizability and therapeutic usefulness. To validate and expand on these findings, future research should use objective PCO grading systems, broader inclusion criteria, and thorough adverse event monitoring. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.