Indocyanine Green (ICG) fluorescence imaging has emerged as a valuable tool in various surgical fields, including endoscopic pituitary surgery. ICG is a near-infrared fluorescent tricarbocyanine dye, approved by the Food and Drug Administration (FDA) in 1959, and is commonly used for diagnostic purposes in cardiocirculatory and hepatic function assessments. ICG’s unique properties, including its peak excitation at 800 nm and rapid hepatic clearance, make it ideal for real-time surgical imaging [1]. ICG is predominantly used for real-time visualisation of blood vessels and assessment of cerebral perfusion, offering a non-invasive, safe, cost-effective, and easily repeatable method to provide instantaneous information for intraoperative decision-making. This technique has been applied to various diseases, including vascular conditions like aneurysms and arteriovenous malformations, and tumours such as cavernous angiomas, meningiomas, and adenomas, enhancing the visualisation of tumour margins, vascular structures, and normal pituitary tissue.

The utility of ICG fluorescence has been affirmed across the broader field of skull base surgery. A recent consensus paper by Suero Molina et al. [2], published by the EANS Skull Base Section, outlined standardised recommendations for fluorescence-guided neurosurgery using ICG. The authors emphasised optimisation of ICG dosing, timing, and workflow for reliable intraoperative vascular and perfusion imaging, while acknowledging emerging delayed-window applications for tumour delineation in pituitary and skull-base surgery. Furthermore, the adoption of endoscope-integrated ICG (e-ICG) in endonasal approaches was promoted in Catapano et al. [3], noting its multimodal use for real-time visualisation of vascular structures and normal tissue preservation.

While ICG's utility in vascular and hepatic imaging is well-established, its adaptation to pituitary surgery hinges on overcoming unique anatomical challenges, such as the gland's proximity to the cavernous sinus and optic apparatus. Endoscopic transsphenoidal surgery (TSS) is a widely adopted and effective approach for the removal of pituitary tumours, offering a panoramic and high-resolution view of the surgical field. However, accurate intraoperative identification and differentiation of tumour margins from surrounding normal structures and critical neurovascular tissues remain challenging. This challenge is exacerbated by the proximity of critical neurovascular structures, where even minor deviations risk carotid injury or pituitary dysfunction [4]. Conventional intraoperative decision-making is often based on the surgeon’s experience and subjective evaluation of tissue characteristics, which can be inconsistent. While objective methods for rapid intraoperative diagnosis exist, they are often technically demanding, require additional time and resources, and are not always reliable. Consequently, there is a persistent need for a simple, reliable method for tissue and structure identification that can provide real-time information without disrupting surgical observation or manipulation [5].

The integration of ICG fluorescence into endoscopic systems presents an innovative solution to these challenges, as it provides intraoperative visualisation that enhances tumour resection and pituitary gland preservation. Recent studies highlight potential advantages over white-light endoscopy for delineating adenoma margins, though specificity varies by technique and timing [6]. Three principal techniques have evolved: the bolus method (early vascular or “flow-based” phase), the Delayed-Window ICG (DWIG) technique, and the Second-Window ICG (SWIG) technique, both of which exploit delayed permeability-related retention. These distinctions reflect the dual physiological mechanisms underlying ICG imaging – an early vascular phase reflecting blood-flow dynamics and a delayed parenchymal phase reflecting tissue permeability [[5], [6], [7], [8], [9]]. Because ICG has a short plasma half-life of approximately 3 min and falls to about 10% of its circulating concentration after 20 min, the intravascular contribution to signal declines steeply and any visual differences attributable purely to flow become indistinguishable beyond that period, whereas delayed-phase fluorescence therefore depends on retention effects within the tumour microenvironment and intentionally exploits retention-based contrast [[5], [6], [7],9,10]. This physiological basis underlies the diagnostic separation between bolus-based vascular visualisation and permeability-based DWIG/SWIG imaging used in pituitary surgery. This mechanistic framing aligns with the broader skull-base guidance emphasised by Suero Molina et al. [2] and provides the rationale for timing choices in pituitary surgery. Variations in dosing, timing, and equipment are noted, yet the findings consistently support ICG’s role in optimising anatomical and functional landmarks during surgery.

Therefore, this systematic review aimed to evaluate the efficacy, reliability, and clinical outcomes of ICG in endoscopic pituitary surgery, based on data from 11 studies conducted across various countries, including Japan, the USA, and Italy. A systematic analysis of the studies was specifically conducted to identify trends, commonalities, and discrepancies in study design, patient demographics, ICG application, visualisation quality, and surgical outcomes, thereby assessing the role of ICG in endoscopic pituitary surgery.

A recent systematic review by Olesrud et al. [11] focused on device generations and protocol heterogeneity for endoscope-integrated ICG in pituitary neuroendocrine tumours (PitNET) surgery. Here, we complement that work by providing a clinically oriented, technique-stratified analysis (bolus, DWIG, SWIG) that synthesises visualisation success, resection and endocrine outcomes, and complications. In this context, “technique-stratified analysis” refers to stratification by ICG administration technique – bolus (flow-based), DWIG (minutes after injection), and SWIG (high-dose 5 mg/kg administered 16−30 hours preoperatively) – to compare performance by protocol. This framework explicitly links fluorescence metrics to intraoperative decision-making and future standardisation [11]. We also situate our synthesis within the wider skull-base evidence base by referencing contemporary systematic guidance that calls for harmonised dosing, timing, and reporting standards [2].