Illuminating the future: assessing probe-based near-infrared autofluorescence for parathyroid detection in endocrine surgery

Postoperative hypoparathyroidism remains one of the most persistent and significant complications of thyroid and parathyroid surgery. Despite the refined precision of modern endocrine surgery, inadvertent injury or removal of parathyroid glands (PGs) continues to occur, leading to transient or permanent hypocalcemia that may significantly affect quality of life (1). The ability to identify and preserve PGs intraoperatively is therefore central to surgical safety and outcomes. Yet, even in the hands of experienced surgeons, visual identification remains subjective, constrained by anatomical variability, and occasionally unreliable (2).

Over the last decade, near-infrared autofluorescence (NIRAF) has emerged as a promising technological adjunct designed to facilitate real-time PG identification. The PG’s intrinsic autofluorescence signal—detected at around 820 nm when stimulated at around 785 nm—allows tissue differentiation without exogenous dyes or contrast agents (3). Early feasibility studies demonstrated high sensitivity and specificity, leading to the development of image-based and probe-based systems now integrated into clinical practice in several high-volume centers (4-6).

In their recent multicenter randomized clinical trial published in JAMA Surgery, Cousart et al. evaluated the performance of a probe-based NIRAF system (PTeye, Medtronic) during thyroidectomy and parathyroidectomy (7). The study represents one of the largest efforts to date to assess this technology across several institutions and varying levels of surgical experience. Rather than presenting a disruptive innovation, the trial offers a careful and pragmatic assessment of how NIRAF may contribute to parathyroid detection in real-world conditions. Its strength lies in the methodological rigor and scale of the investigation, providing valuable data on device reproducibility and surgeon usability rather than proposing to redefine endocrine surgery practice.

Since its first description by Paras et al. in 2011, NIRAF has evolved from an experimental observation into a practical intraoperative tool for endocrine surgeons (8). The earliest systems were probe-based, which rely on contact probes capable of quantifying autofluorescence intensity ratios between suspected PGs and surrounding tissue (3,4). This technique offers a portable and objective solution, providing reproducible intraoperative feedback particularly useful in deep or obscured surgical fields. These studies established the fundamental optical signature of parathyroid tissue and demonstrated the feasibility of label-free, real-time identification during surgery. The PTeye system, derived from this foundational work, subsequently became the first probe-based platform to receive Food and Drug Administration (FDA) approval for intraoperative parathyroid detection (4).

Building on these findings, image-based systems were subsequently designed to provide wide-field visualization, allowing surgeons to map autofluorescent signals across the operative field. This approach facilitated real-time anatomical orientation and was progressively adopted in specialized centers for thyroid and parathyroid surgery. The PARAFLUO trial demonstrated that intraoperative NIRAF imaging reduced transient postoperative hypocalcemia by enabling earlier and more consistent gland recognition (9). Subsequent multicenter studies have confirmed improved parathyroid detection and greater surgeon confidence using both probe- and image-based NIRAF technologies in diverse operative settings (10-12).

Despite this progress, most prior data on NIRAF originated from single-center or surgeon-specific series, often characterized by heterogeneity in methodology and limited sample size (13,14). These constraints have restricted the generalizability of findings and underscored the need for larger, collaborative evaluations. The trial by Cousart et al. therefore represents a valuable contribution toward addressing these gaps by testing the technology across multiple U.S. institutions and surgeons with varying levels of experience in a randomized, pragmatic design (8).

In this multicenter trial, 752 patients undergoing parathyroidectomy or total/completion thyroidectomy were randomized to either standard surgery or surgery assisted by NIRAF. The primary endpoint was the mean number of PGs identified intraoperatively with high confidence, while secondary endpoints included postoperative hypoparathyroidism (transient and persistent), operative time, frozen section utilization, and inadvertent parathyroidectomy. The study demonstrated that NIRAF significantly increased the number of PGs identified during bilateral exploration parathyroidectomy and total thyroidectomy. For bilateral parathyroidectomy, surgeons identified an average of 3.5 glands per patient using NIRAF vs. 3.2 in controls (P<0.001). During thyroidectomy, the mean number of glands detected was 3.3 with NIRAF compared to 2.8 without (P<0.001). These results confirm that NIRAF enhances intraoperative gland visualization, particularly in complex or bilateral procedures.

Interestingly, although the rate of transient and permanent hypoparathyroidism did not differ significantly between groups, there was a reduction in definitive cases—from 6 (3.4%) in the control arm to 3 (1.7%) with NIRAF assistance. While this trend did not reach statistical significance, it may reflect the limited number of events in this high-volume, expert surgical cohort, where baseline complication rates are already low. Operative duration and hospital stay were comparable. However, the authors reported a marked reduction in frozen section usage, especially during thyroidectomy (4% vs. 11.2%, P=0.01), suggesting an efficiency benefit and cost-saving potential. Moreover, the technology substantially improved surgeons’ confidence in gland identification. These findings support the emerging consensus that NIRAF enhances recognition and surgeon confidence, although its measurable impact on long-term functional outcomes remains limited.

The results of Cousart et al. therefore reinforce that NIRAF serves as a valuable intraoperative adjunct, improving anatomical identification but not necessarily translating into lower hypoparathyroidism rates. Previous trials have shown comparable trends, confirming better intraoperative recognition without consistent improvement in postoperative calcium or parathormone levels (9-11). By validating a probe-based NIRAF system in a large, multicenter setting, this study confirms the reproducibility and practicality of the technology across diverse surgical environments, while emphasizing that anatomical identification alone may not guarantee functional preservation.

Beyond confirming reproducibility, the trial also provides insight into how the technology performs relative to surgeon experience. Senior surgeons derived measurable benefit from NIRAF in bilateral explorations, while junior surgeons showed more modest improvements. Although this result may appear unexpected, it likely reflects the ability of experienced surgeons to better integrate optical feedback into their intraoperative decision-making, whereas less experienced surgeons tend to rely more on conventional visual assessment. The most pronounced gains were observed among surgical trainees, who demonstrated higher accuracy and confidence when using the technology. Together, these findings highlight that NIRAF should be viewed as a supportive tool—rather than a substitute for surgical expertise and intraoperative judgment—that can enhance parathyroid identification and serve as an educational aid by providing objective, real-time feedback to support the acquisition of anatomical and technical skills in endocrine surgery.

Preserving parathyroid function requires not only accurate identification but also adequate vascularization—a critical factor that cannot be inferred from autofluorescence alone. While indocyanine green (ICG) angiography has been proposed as a complementary tool to assess gland perfusion, as demonstrated by Demarchi et al. (15), its use must necessarily follow NIRAF-based identification, as ICG administration may interfere with autofluorescence detection because of spectral overlap. These limitations have stimulated interest in dye-free optical approaches capable of assessing parathyroid perfusion or viability without contrast agents. Label-free techniques, including diffuse reflectance spectroscopy and laser speckle contrast imaging, have recently been explored for this purpose, aiming to provide real-time functional information alongside anatomical identification (16,17). Although such strategies appear promising, standardized intraoperative decision-making algorithms integrating viability assessment are still lacking and warrant further investigation.

From an educational perspective, NIRAF may also play a role beyond gland detection. By providing real-time optical feedback, it transforms parathyroid identification into a measurable and teachable skill, potentially facilitating structured learning and intraoperative decision-making. As such, the technology could complement traditional mentorship and enhance standardization in endocrine surgery training. Nevertheless, broader adoption will depend on practical considerations, including device costs, calibration time, and surgeon familiarity. The absence of proven clinical benefit still challenges the justification for routine use, emphasizing the need for future cost-effectiveness studies and identification of patient populations most likely to benefit.

Cousart et al.’s study is not without limitations. Variability in surgical technique among centers, the lack of standardized assessment of excised specimens, and the overall low incidence of hypocalcemia limit the ability to draw firm conclusions regarding outcome improvements. Furthermore, as the trial focused primarily on intraoperative identification rather than postoperative endpoints, long-term data on parathyroid function and cost-effectiveness remain lacking. Despite these constraints, the trial’s multicenter design and inclusion of surgeons at different experience levels make it a valuable contribution to the field and a methodological reference for future research. This aligns with previous reflections, which emphasized that while probe-based autofluorescence enhances detection accuracy, it should be viewed as one element within a broader multimodal strategy aimed at functional preservation (18).

To conclude, the overall evidence across both image- and probe-based studies remains remarkably consistent. On average, the use of NIRAF allows surgeons to identify approximately 0.5 additional PGs per patient—representing a 10–15% improvement in detection compared with visual inspection alone. While individual randomized trials have generally failed to demonstrate statistically significant reductions in postoperative hypoparathyroidism, recent meta-analyses aggregating data from more than 5,000 patients indicate that these benefits become significant when pooled, confirming lower rates of transient hypocalcemia and suggesting a trend toward reduced permanent hypoparathyroidism (19,20). Together, these findings suggest that the true clinical value of NIRAF may only emerge when data are interpreted at scale, reflecting cumulative and reproducible gains in parathyroid preservation.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Gland Surgery. The article has undergone external peer review.

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-aw-540/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2025-aw-540/coif). F.T. reports consulting fees, honoraria for lectures, presentations and support for attending meeting and/or travels from Medtronic and Getinge/Fluoptics, paid to the institution. The other author has no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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