UNASSIGNED: Near-infrared autofluorescence (NIRAF) utilizes the natural autofluorescence of parathyroid glands (PGs) to improve their identification during thyroid surgeries, reducing the risk of inadvertent removal and subsequent complications such as hypoparathyroidism. This study evaluates NIRAF\'s effectiveness in real-world surgical settings, highlighting its potential to enhance surgical outcomes and patient safety.
UNASSIGNED: We evaluate the effectiveness of NIRAF in detecting PGs during thyroidectomy and central neck dissection and investigate autofluorescence characteristics in both fresh and paraffin-embedded tissues.
UNASSIGNED: We included 101 patients diagnosed with papillary thyroid cancer who underwent surgeries in 2022 and 2023. We assessed NIRAF\'s ability to locate PGs, confirmed via parathyroid hormone assays, and involved both junior and senior surgeons. We measured the accuracy, speed, and agreement levels of each method and analyzed autofluorescence persistence and variation over 10 years, alongside the expression of calcium-sensing receptor (CaSR) and vitamin D.
UNASSIGNED: NIRAF demonstrated a sensitivity of 89.5% and a negative predictive value of 89.1%. However, its specificity and positive predictive value (PPV) were 61.2% and 62.3%, respectively, which are considered lower. The kappa statistic indicated moderate to substantial agreement (kappa = 0.478; P < 0.001 ). Senior surgeons achieved high specificity (86.2%) and PPV (85.3%), with substantial agreement (kappa = 0.847; P < 0.001 ). In contrast, junior surgeons displayed the lowest kappa statistic among the groups, indicating minimal agreement (kappa = 0.381; P < 0.001 ). Common errors in NIRAF included interference from brown fat and eschar. In addition, paraffin-embedded samples retained stable autofluorescence over 10 years, showing no significant correlation with CaSR and vitamin D levels.
UNASSIGNED: NIRAF is useful for PG identification in thyroid and neck surgeries, enhancing efficiency and reducing inadvertent PG removals. The stability of autofluorescence in paraffin samples suggests its long-term viability, with false positives providing insights for further improvements in NIRAF technology.

Inflammation plays a key role in the induction of choroidal neovascularization (CNV). Inflammatory choroidal neovascularization (iCNV) is a severe but uncommon complication of both infectious and non-infectious uveitides. It is hypothesized that its pathogenesis is similar to that of wet age-related macular degeneration (AMD), and involves hypoxia as well as the release of vascular endothelial growth factor, stromal cell-derived factor 1-alpha, and other mediators. Inflammatory CNV develops when inflammation or infection directly involves the retinal pigment epithelium (RPE)-Bruch\'s membrane complex. Inflammation itself can compromise perfusion, generating a gradient of retinal-choroidal hypoxia that additionally promotes the formation of choroidal neovascularization in the course of uveitis. The development of choroidal neovascularization may be a complication, especially in conditions such as punctate inner choroidopathy, multifocal choroiditis, serpiginous choroiditis, and presumed ocular histoplasmosis syndrome. Although the majority of iCNV cases are well defined and appear as the \"classic\" type (type 2 lesion) on fluorescein angiography, the diagnosis of iCNV is challenging due to difficulties in differentiating between inflammatory choroiditis lesions and choroidal neovascularization. Modern multimodal imaging, particularly the recently introduced technology of optical coherence tomography (OCT) and OCT angiography (noninvasive and rapid imaging modalities), can reveal additional features that aid the diagnosis of iCNV. However, more studies are needed to establish their role in the diagnosis and evaluation of iCNV activity.

BACKGROUND: Iatrogenic injury of the parathyroid glands is the most frequent complication after total thyroidectomy.
OBJECTIVE: To determine the effectiveness of near-infrared autofluorescence (NIRAF) in reducing postoperative hypocalcemia following total thyroidectomy.
METHODS: PubMed, Scopus, and Google Scholar databases were searched. Randomised trials reporting at least one hypocalcemia outcome following total thyroidectomy using NIRAF were included.
RESULTS: The qualitative data synthesis comprised 1363 patients from nine randomised studies, NIRAF arm = 636 cases and non-NIRAF arm = 637 cases. There was a statistically significant difference in the overall rate of hypocalcemia log(OR) = -0.7 [(-1.01, -0.40), M-H, REM, CI = 95%] and temporary hypocalcemia log(OR) = -0.8 [(-1.01, -0.59), M-H, REM, CI = 95%] favouring the NIRAF. The difference in the rate of permanent hypocalcemia log(OR) = -1.09 [(-2.34, 0.17), M-H, REM, CI = 95%] between the two arms was lower in the NIRAF arm but was not statistically significant.
CONCLUSIONS: NIRAF during total thyroidectomy helps in reducing postoperative hypocalcemia. Level of evidence-1.

Hypoparathyroidism is the most frequent complication in thyroid surgery. The aim of this study was to evaluate the impact of intraoperative parathyroid gland identification, using autofluorescence imaging, on the rate of post-operative (PO) hypoparathyroidism in thyroid cancer surgery. Patients undergoing total thyroidectomy with central neck dissection from 2018 to 2022 were included. A prospective cohort of 77 patients operated on using near-infrared autofluorescence (NIRAF+) with the Fluobeam® (Fluoptics, Grenoble, France) system was compared to a retrospective cohort of 94 patients (NIR-). The main outcomes were the rate of PO hypocalcemia, with three cutoffs: corrected calcium (Cac) < 2.10 mmol/L, <2.00 mmol/L and <1.875 mmol/L, and the rate of permanent hypoparathyroidism, at 12 months. The rate of PO Cac < 2.10 mmol/L was statistically lower in the NIRAF+ group, compared to the control group (36% and 60%, p = 0.003, respectively). No statistically significant difference was observed for the other two thresholds. There was a lower rate of permanent hypoparathyroidism in the NIRAF+ group (5% vs. 14% in the control group), although not statistically significant (p = 0.07). NIRAF is a surgically non-invasive adjunct, and can improve patients\' outcomes for thyroid cancer surgery by reducing post-operative temporary hypoparathyroidism. Larger prospective studies are warranted to validate our findings.

BACKGROUND: Primary adenoma (PA) and multi-gland hyperplasia (MGH) account for 85% and 15% of primary hyperparathyroidism (PHPT) cases, respectively. Near-infrared autofluorescence (NIRAF) enhances intraoperative parathyroid identification. We hypothesized that PA would display a more heterogeneous NIRAF pattern compared to MGH.
METHODS: Patients undergoing surgery for sporadic PHPT were categorized based on the presence of PA or MGH. To quantify heterogeneity, we utilized ratios of (1) mean parathyroid gland (PG) NIRAF over background NIRAF (mean ratio), (2) minimum and (3) maximum PG NIRAF over mean PG NIRAF (minimum and maximum ratios). Additionally, a heterogeneity score was quantified using mean ratio (mean PG NIRAF over background NIRAF), and overall NIRAF (mean NIRAF of eight random 15 × 15 pixel areas). A point was assigned to ratios <0.8 or >1.2. Images were quantified by ImageJ software. Mann-Whitney test was performed for all comparisons.
RESULTS: Of 78 patients, 63 had a single PA and 15 had MGH, totaling 102 PGs. There was no difference between their mean ratios. PA had a lower minimum ratio compared to that of MGH (0.86 ± 0.01 vs. 0.93 ± 0.01, p = 0.001) and a brighter maximum ratio (1.21 ± 0.02 vs. 1.12 ± 0.01, p = 0.0008). PA also scored higher on their heterogeneity scores compared to MGH (1.27 ± 0.23 vs. 0.33 ± 0.15, p = 0.001).
CONCLUSIONS: Single parathyroid adenomas display a more heterogeneous autofluorescence pattern compared to that of multi-gland hyperplasia. Intraoperative characterization of PGs by real-time NIR imaging patterns may be a beneficial adjunct during parathyroid surgery.

Treatment options for thyroid pathologies have expanded to include scarless and remote access methods such as the transoral endoscopic thyroidectomy vestibular approach (TOETVA). Currently, no standardized methods exist for locating parathyroid glands (PGs) in patients undergoing TOETVA, which can lead to parathyroid injury and subsequent hypocalcemia. This early feasibility study describes and evaluates the hANDY-i endoscopic attachment for detecting PGs in transoral thyroidectomy.
We used a prototype parathyroid autofluorescence imager (hANDY-i) that was mounted to a 10-mm 0-degree endoscope. The device delivers a split screen view of Red-green-blue (RGB) and near-infrared autofluorescence (NIRAF) which allows for simultaneous anatomical localization and fluorescence visualization of PGs during endoscopic thyroid dissection.
One cadaveric case and two patient cases were included in this study. The endoscopic hANDY-i imaging system successfully visualized PGs during all procedures.
The ability to leverage parathyroid autofluorescence during TOETVA may lead to improved PG localization and preservation. Further human studies are needed to assess its effect on postoperative hypocalcemia and hypoparathyroidism.

Postoperative hypoparathyroidism may cause significant patient morbidity and even mortality. Emerging technologies centered on autofluorescent properties of parathyroid glands when exposed to near-infrared light hold promise to improve surgical parathyroid gland identification and preservation. Two systems (probe-based and camera-based) are commercially available currently; however, neither system alone provides indication of vascular viability or postoperative parathyroid gland function. The administration of indocyanine green, when combined with near-infrared fluorescence imaging, enables subjective assessment of parathyroid gland perfusion. Additional technologies to assess parathyroid gland perfusion are being developed. The impact of these nascent technologies on relevant clinical outcomes is an area of active investigation.

Near-infrared light can penetrate the fat or connective tissues overlying the parathyroid gland (PG), enabling early localization of the PG by near-infrared autofluorescence (NIRAF) imaging. However, the depth at which the PG can be detected has not been reported. In this study, we investigated the detectable depth of unexposed PGs using NIRAF during thyroidectomy.
Fifty-one unexposed PGs from 30 consecutive thyroidectomy patients, mapped by an experienced surgeon (K.D. Lee) with the use of NIRAF imaging, were included. For NIRAF detection of PGs, a lab-built camera imaging system was used. Detectable depths of the unexposed PGs were measured using a Vernier caliper. The NIRAF images were classified as faint or bright depending on whether a novice could successfully interpret the image as showing the PG. Data on variables that may affect detectable depth and NIRAF intensity were collected.
Detectable depth ranged between 0.35 and 3.05 mm, with a mean of 1.23 ± 0.73 mm. The average NIRAF intensity of unexposed PGs was 3.13 au. After dissection of the overlying tissue, the intensity of the exposed PG increased to 4.88 au (p < 0.001). No difference in NIRAF intensity between fat-covered (3.27 ± 0.90 au) and connective tissue-covered PGs (3.00 ± 1.23 au) was observed (p = 0.369). PGs covered by fat tissue (depth: 1.77 ± 0.67 mm) were found at deeper locations than those covered by connective tissue (depth: 0.70 ± 0.21 mm) (p < 0.001). The brightness of images of the faint group (2.14 ± 0.48 au) was on average 1.24 au lower than that of the bright group (3.38 ± 1.04 au) (p = 0.001). A novice successfully localized 80.4% of the unexposed PGs. Other variables did not significantly affect detectable depth.
Unexposed PGs could be mapped using NIRAF imaging at a maximum depth of 3.05 mm and an average depth of 1.23 mm. A novice was able to localize the PGs before they were visible to the naked eye at a high rate. These results can be used as reference data for localization of unexposed PGs in thyroid surgery.

UNASSIGNED: Autosomal Recessive Bestrophinopathy (ARB) is an inherited retinal disease caused by biallelic mutations in the BEST1 gene. Herein, we report the multimodal imaging findings of ARB presenting with cystoid maculopathy and investigate the short-term response to combined systemic and topical carbonic anhydrase inhibitors (CAIs).
UNASSIGNED: An observational, prospective, case series on two siblings affected by ARB is presented. Patients underwent genetic testing and optical coherence tomography (OCT), blue-light fundus autofluorescence (BL-FAF), near-infrared fundus autofluorescence (NIR-FAF), fluorescein angiography (FA), MultiColor imaging, and OCT angiography (OCTA).
UNASSIGNED: Two male siblings, aged 22 and 16, affected by ARB resulting from c.598C>T, p.(Arg200*) and c.728C>A, p.(Ala243Glu) BEST1 compound heterozygous variants, presented with bilateral multifocal yellowish pigment deposits scattered through the posterior pole that corresponded to hyperautofluorescent deposits on BL-FAF. Vice versa, NIR-FAF mainly disclosed wide hypoautofluorescent areas in the macula. A cystoid maculopathy and shallow subretinal fluid were evident on structural OCT, albeit without evidence of dye leakage or pooling on FA. OCTA demonstrated disruption of the choriocapillaris throughout the posterior pole and sparing of intraretinal capillary plexuses. Six months of combined therapy with oral acetazolamide and topical brinzolamide resulted in limited clinical benefit.
UNASSIGNED: We reported two siblings affected by ARB, presenting as non-vasogenic cystoid maculopathy. Prominent alteration of NIR-FAF signal and concomitant choriocapillaris rarefaction on OCTA were noted in the macula. The limited short-term response to combined systemic and topical CAIs might be explained by the impairment of the RPE-CC complex.

OBJECTIVE: The purpose of this single-blinded, 2-centre, randomized controlled trial was to test if near-infrared (NIR) autofluorescence image guidance for parathyroid gland (PG) detection during total thyroidectomy can reduce the incidence of hypoparathyroidism in both malignant and benign cases.
METHODS: Patients admitted for primary or completion total thyroidectomy were randomized to either the NIR intervention group or the standard care NONIR (no near infrared) group. The primary endpoint was the rate of hypoparathyroidism at the 3-month follow-up, defined as hypocalcemia and inappropriately low parathyroid hormone levels and/or continuous treatment with active vitamin D. The secondary endpoint was the PG identification rate.
RESULTS: A total of 147 patients were included of whom 73 were allocated to NIR. Primary or completion thyroidectomy was conducted in 84 and 63 cases, respectively. A total of 130 completed 3 months follow-up. Postoperative hypoparathyroidism in the NIR group at 12 h, 1 month and 3 months was, respectively, 31.8, 14.1, 6.5% compared with 35.9, 18.9, 11.8% in the NONIR group (all p > 0.46). In the NIR group, the identification rate of PGs was 69.5% (146 of 210 PGs), and 9% (19 of 210 PGs) were identified only due to additional use of NIR. For 15 out of 69 patients (21.7%) additionally PGs was found.
CONCLUSIONS: Hypoparathyroidism was nominally less frequent in the NIR group, although not statistically significant. Further studies are needed to confirm if NIR may be a supportive PG identification tool to minimize the number of PG which would have been otherwise missed, especially during more complicated thyroid procedures.
BACKGROUND: ClinicalTrials.gov: NCT04193332. Registration date: 16.08.2019.