Near infrared autofluorescence for parathyroid detection during thyroid and parathyroid surgery: a valuable medical device but not a substitute for surgical experience and volume

Thyroid and parathyroid surgery have substantially evolved over the last decades as a result of surgical innovations such as intraoperative vagal and recurrent laryngeal nerve monitoring and energy-based haemostatic devices, only to mention a few. Such innovations have provided useful intraoperative adjuncts to surgeons and, in doing so, led to improvement in patient care (1,2).

It is known that nearly all patients undergoing thyroid surgery exhibit a reduction in parathyroid hormone (PTH) levels to some degree, a subgroup of whom fall below the lower limit of normal. Most of these patients demonstrate recovery (transient hypoparathyroidism), whereas for some, there is persistence (permanent hypoparathyroidism) (3). A key aspect of thyroid surgery therefore entails the identification and preservation of the parathyroid glands. Inadvertent removal (or devascularisation) of the parathyroid glands can result in severe hypocalcaemia and/or hypoparathyroidism, a serious complication that, untreated, can be life-threatening and, if permanent, can have a detrimental effect on patients’ quality of life (QoL) (4). 
Similarly, when it comes to parathyroid surgery, especially during bilateral cervical exploration, identifying all parathyroid glands is paramount to ensure that the patient is cured of their hyperparathyroidism and prevent the need for revision surgery.

As a result, numerous technological adjuncts have been introduced for the intraoperative identification of the parathyroid glands, with examples including frozen section analysis and intraoperative PTH assay to confirm correct gland removal during parathyroidectomy (5,6). Another technology for intraoperative parathyroid identification is fluorescent-guided surgery (FGS) with or without indocyanine green (ICG) fluorescence (7,8). However, despite the above, hypoparathyroidism remains one of the commonest complications following total/completion thyroidectomy (9).

Near infrared autofluorescence (NIRAF) constitutes the latest addition to the armamentarium of intraoperative parathyroid identification technologies. Contrary to ICG fluorescence, NIRAF is dye-free thus obviating the risk of allergic reactions. Depending on the manufacturer, NIRAF technology can be image-based or fibre-based, with the former involving a handheld NIRAF camera for visual identification of the parathyroid glands whilst the latter consists of a 4 mm fibre tip to objective quantify parathyroid autofluorescence. In addition to its safety profile, NIRAF has been shown to be a promising technological innovation when it comes to intraoperative parathyroid gland identification (10).

The value of NIRAF in both thyroid and parathyroid surgery was assessed in a recent multicentre randomised controlled trial (RCT) by Cousart et al. utilising the fibre-based NIRAF system PTeye^TM (Medtronic, Minneapolis, MN). Following enrolment of 1,223 patients from 4 high-volume centres across the US between March 2020 and July 2024, 754 patients were randomised 1:1 to receive NIRAF or not during thyroidectomy (n=354) and parathyroidectomy (n=400) procedures. The primary outcome involved the mean number of parathyroid glands identified intraoperatively whilst the secondary outcome related to postoperative hypoparathyroidism rates, both transient and at last follow-up (11).

In the thyroidectomy group, the utilisation of NIRAF was shown to result in a higher number of parathyroid glands identified per patient. Although it can be challenging to extrapolate the significance of this finding when it comes to clinical outcomes, it can be postulated that increasing the number of parathyroid glands identified during thyroidectomy will likely have a favourable impact on postoperative hypoparathyroidism rates. It is important to note that no difference in hypoparathyroidism rates was found between the NIRAF and control groups (11,12). When looking at the literature, recent meta-analyses of RCTs showed that use of NIRAF led to a reduced risk of both post-operative hypocalcaemia and persistent hypoparathyroidism following thyroidectomy (10,13). This discrepancy between findings may be, in part, explained by the pathogenesis of hypoparathyroidism. A recent paper has postulated that fluid accumulation in the thyroid resection bed contributes to a reduced sensitivity to hypocalcaemia post-surgery, reflecting secretory insufficiency of the parathyroid glands (14). This has been thought to be due to this wound fluid activating the calcium-sensing receptor (CaSR) within the parathyroid parenchyma to suppress PTH secretion (15).

In the parathyroidectomy group, the utilisation of NIRAF was also shown to result in a higher number of parathyroid glands identified per patient during bilateral cervical exploration but not for focused parathyroidectomy. It would thus be safe to argue that by increasing the number of parathyroid glands identified intraoperatively, NIRAF adds value to 4-gland exploration procedures where it can be challenging to locate all 4 parathyroid glands and failure to do so bears a high risk of failure and need for re-operative parathyroidectomy (16,17).

Interestingly, in a subgroup analysis evaluating the primary outcome by experience level, it was found that the use of NIRAF during bilateral cervical exploration increased the number of parathyroid glands identified by senior surgeons. This did not hold true for junior surgeons. Similarly, the use of NIRAF during focused parathyroidectomy only increased the number of parathyroid glands identified by senior surgeons but not by juniors. The same applied for thyroidectomy where senior surgeons consistently identified more parathyroid glands with the aid of NIRAF whilst junior surgeons exhibited more variable results. This is critical as it points to the fact that NIRAF is no substitute to surgical experience and volume, with its value only proven when used by senior surgeons as an adjunctive tool to aid in the identification of parathyroid tissue already visually located by the surgeon. On the other hand, NIRAF constitutes a valuable training tool with trainee surgeons demonstrating the most significant improvements in both study arms.

Another important finding of this RCT encompasses the fact that the use of NIRAF did not add to operative time in either the thyroidectomy or parathyroidectomy groups. Moreover, in the thyroidectomy group, NIRAF use resulted in lower numbers of frozen section required to confirm parathyroid tissue. This bears important implications as frozen section analysis adds to operative time, cost, and has resource implications through the additional need of a histopathologist being available on site at the time of surgery.

In conclusion, this latest multicentre RCT has shown that fibre-based NIRAF adds value to both thyroid and parathyroid surgery when it comes to the number of parathyroid glands identified intraoperatively without increasing operative time and, for thyroidectomy, its use was shown to also reduce the need for frozen section analysis. However, the use of NIRAF should not be considered a substitute for surgical experience and volume, a statement also supported by this study’s findings as the improvement in the number of parathyroid glands identified intraoperatively with NIRAF only applied to senior surgeons and not juniors. Though promising, further research is needed to establish the role of fibre-based NIRAF in post-operative hypoparathyroidism rates both in the short- and long-term and its associated cost effectiveness. Finally, artificial intelligence (AI) is already being trialled to augment NIRAF’s role in intraoperative parathyroid detection, an innovation that may prove of special value for junior surgeons and those practicing in lower volume centres (18).

Supplementary

The article’s supplementary files as

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.