A Systematic and Narrative Review of Safety and Complications in Minimally Invasive Glaucoma Surgery (MIGS) Between 2014–2024 [Response to Letter]

Dear editor

We thank Nagy et al for their interest in our review and for the opportunity to clarify this point. Their correspondence concerns the reporting of the first-in-human FLIGHT study in Table 1 of our article.

We would first like to emphasize that the body of our manuscript already describes the FLIGHT findings in the terms used by the original study. Specifically, we reported that the most common postoperative event was blood reflux into the anterior chamber, observed in 11 of 18 eyes (61.1%) within the first two postoperative hours, visible only under gonioscopy, resolving by postoperative day one, and without impact on vision. We further stated that no serious laser-related adverse events were reported.

The purpose of Table 1, however, was not to reproduce verbatim the terminology of each individual primary report, but rather to provide a cross-technique, pooled overview of reported safety events across a highly heterogeneous body of literature. As stated throughout the manuscript, one of the principal limitations of this review is the lack of harmonization in complication definitions and reporting across studies. We noted that common events such as hyphema and IOP spikes are inconsistently defined and reported across studies. Accordingly, caution is required when interpreting pooled incidence rates.

The definition of hyphema itself differs substantially across publications. In many studies, it remains unclear whether reported rates refer to microscopic or intraoperative blood reflux that is self-limited and bears little clinical significance, or to clinically apparent, persistent hyphema. Although such transient reflux may fall within the broader spectrum of hyphema, it differs fundamentally from clinically significant hemorrhagic events in both mechanism and clinical relevance. However, these distinctions are often not clearly delineated in published reports. This lack of granularity makes strict categorization across studies unreliable and, in practice, leaves no alternative but to pool hemorrhagic events under a common label for the purpose of synthesis. The narrative component of the review is therefore essential to provide context and nuance where available, as is the case for the FLIGHT study.

Across several MIGS categories, blood reflux, microhyphema, or transient anterior chamber bleeding are variably described depending on study design and author preference. In our review, for example, we highlighted that in ab interno canaloplasty, intraoperative hyphema is often considered a marker of successful catheterization rather than a complication, and that in iStent inject studies, blood reflux may be regarded as a desirable sign of patent distal outflow, leading some authors not to report it, while others report rates approaching 100%. Therefore, modifying the classification for the FLIGHT study alone would introduce an interpretative imbalance relative to other techniques presented in the same table.

Accordingly, Table 1 should be interpreted as a harmonized summary table rather than a substitute for the detailed narrative analysis of each procedure. In this context, the inclusion of the FLIGHT events under a broader hemorrhagic category reflects an editorial pooling decision made for consistency with the broader MIGS literature, in which primary studies often do not clearly distinguish between intraoperative reflux, transient blood reflux, microhyphema, and clinically significant postoperative or persistent hyphema.

We therefore respectfully disagree that the review contains a factual contradiction requiring formal correction. The original FLIGHT observation was described accurately in the main text, including its transient and clinically benign nature, and the limitations of pooled incidence rates reported in Table 1 are clearly discussed in the manuscript.

That said, we agree that this point highlights a broader and important issue in MIGS safety reporting: the absence of standardized definitions for hemorrhagic events following angle surgery. As noted in our conclusion, the field would benefit from clearer and more uniform distinctions between: (1) physiological intraoperative or immediate postoperative blood reflux, (2) transient microhyphema or limited hyphema without clinical consequence, and (3) clinically significant, persistent, or intervention-requiring hyphema.

For clarity, we welcome the addition of the following clarification to the caption of Table 1 in Gillmann et al:¹ “Weighted mean incidence of complications following all studied surgical techniques, based on the number of eyes analyzed in this systematic review. Complication rates are presented as percentages, with values >1% shown in bold. Complications are arranged in tiers according to clinical relevance: the top tier includes vision-threatening, structurally destructive, or chronic events; the second tier comprises typically milder or self-limiting events, although they may still be clinically relevant and indicate surgical invasiveness (‘Hyphema’ includes pooled hemorrhagic events across the hyphema spectrum, ranging from transient intraoperative or microscopic reflux to clinically apparent or persistent hyphema); the third tier includes IOP-related events (IOP spikes and hypotony), encompassing the heterogeneous definitions used across studies; and the bottom tier includes device-related adverse events. Color coding reflects clinical concern: green for low incidence, orange for moderate concern, and red for higher clinical concern. Thresholds were set at 1% and 5% for serious complications, and at 10% and 20% for more benign adverse events. ‘Endothelial safety concern’ refers to evidence of endothelial cell loss”.

We believe such a clarification would improve interpretability while preserving methodological consistency across the pooled analysis

In summary, we appreciate the authors’ comment and agree that the distinction between physiological reflux and clinically meaningful hyphema is important. However, this distinction is already addressed in the narrative text, and Table 1 should be interpreted within the context of the full manuscript and its stated methodological limitations.