The efficacy of cryosurgery for skin cancers is believed to depend on thaw time, which may be influenced by the presence of adrenaline in local anaesthetics due to its vasoconstrictive effects. This is the first study to perform detailed, non-invasive temperature measurements using infrared (IR) thermography during cryosurgery for basal cell carcinomas (BCCs), evaluating the impact of adrenaline on thaw time. A total of 15 patients with eyelid BCCs underwent cryosurgery with local anaesthetics both with and without adrenaline. Thawing was continuously monitored using a high-resolution IR camera and compared with the surgeon's visual assessment. No significant difference in thaw time was observed between anaesthetics with and without adrenaline. Thermographic mapping revealed a triphasic thawing curve. The surgeon's visual assessment of thawing corresponded well with the point at which tissue temperatures rose above 0°C, likely indicating the onset of reperfusion, thus providing a clinical margin beyond the actual phase transition. This is the first study to use IR thermography to monitor cryosurgery of BCCs, demonstrating that adrenaline in local anaesthetics does not affect thaw time. The findings suggest that deeper tissue perfusion during BCC treatment may counteract superficial vasoconstriction, supporting the effective use of cryosurgery regardless of adrenaline use.

PURPOSE:To evaluate the feasibility of hyperspectral imaging (HSI) for non-invasive characterization of pathological conditions in the human anterior segment and to explore its use alongside laser speckle contrast imaging (LSCI) for consecutive assessment of oxygenation and perfusion. METHODS:23 patients were examined with HSI and/or LSCI prior to evisceration or enucleation. HSI recorded diffusely backscattered light from the conjunctiva/sclera, iris/cornea, and pupil/retina regions. Spectra were interpreted using reference tissue scattering and absorption signatures from which changes in oxygen saturation and total hemoglobin were determined. LSCI was used to assess perfusion. Spectral and perfusion data from eyes with conjunctival hyperemia, corneal opacity, and corneal hemosiderosis were compared with reference anterior segments. RESULTS:Spectral differences were observed with HSI for the major anatomical regions of the anterior segment. Spectra were interpreted in relation to known chromophore-associated spectral features of the examined tissue. Hyperemic eyes showed an increase in hemoglobin-related absorption, while opaque or hemosiderotic corneas exhibited flattening of the spectra, characteristic of increased light scattering and an obscured melanin absorption. Perfusion demonstrated a high spatial correlation with the signal related to total hemoglobin. In hyperemic eyes, perfusion and total hemoglobin were elevated while oxygen saturation remained stable, indicating compensatory regulation. CONCLUSIONS:This feasibility study demonstrates the potential of HSI for non-invasive characterization of physiologically relevant spectral signatures in the human anterior segment. Together with consecutive LSCI measurements, HSI provides independently acquired physiological insights on perfusion and oxygenation. With larger studies, HSI could reveal how pathological conditions evolve at a biological level.

The incidence of melanoma is rising and will require more efficient diagnostic procedures to meet a growing demand. Excisional biopsy and histopathology is still the standard, which often requires multiple surgical incisions with increasing margins due inaccurate visual assessment of where the melanoma borders to healthy tissue. This challenge stems, in part, from the inability to reliably delineate the melanoma without visually inspecting chemically stained histopathological cross-sections. Spectroscopic imaging have shown promise to non-invasively characterize the molecular composition of tissue and thereby distinguish melanoma from healthy tissue based on spectral features. In this work we describe a computational framework applied to multispectral photoacoustic (PA) imaging data of melanoma in humans and demonstrate how the borders of the tumor can be automatically determined without human input. The framework combines K-means clustering, for an unbiased selection of training data, a one-dimensional convolutional neural network applied to PA spectra for classifying pixels as either healthy or diseased, and an active contour algorithm to finally delineate the melanoma in 3D. The work stands to impact clinical practice as it can provide both pre-surgical and perioperative guidance to ensure complete tumor removal with minimal surgical incisions.

Background/aims It is unclear whether a reduction in tear secretion contributes to the discomfort experienced by those with prosthetic eyes. Tear secretion has hitherto only been measured with the Schirmer test which may be affected by the pooling of tears behind the prosthesis. In this study, direct imaging of the lacrimal gland has been performed to measure tear secretion in anophthalmic sockets. The relation between the area of meibomian glands and dry eye symptoms was also assessed. Methods 12 patients were included. The amount of tear secretion was measured by direct imaging of the lacrimal gland while the presence of meibomian glands was determined using meibography. The 5-item Dry Eye Questionnaire was used to assess symptoms of dry eye. Results No difference was found in tear secretion between the anophthalmic socket and the contralateral eye. The area of meibomian glands was significantly reduced in eyelids on the side of the prosthetic eye, compared with the contralateral eye. Seven patients reported symptoms indicative of dry eye in the anophthalmic socket, compared with only two in the contralateral eye. Conclusions The effects of an eye prosthesis on meibomian glands may contribute to the frequently perceived symptoms of dry eye despite unaffected in tear secretion.

PURPOSE:To evaluate the role of blood perfusion and revascularization during the healing process of periocular defects treated with laissez-faire following tumor excision. METHODS:Ten patients with periocular basal cell carcinomas underwent excision, followed by laissez-faire wound management. Blood perfusion was measured using laser speckle contrast imaging postoperatively. RESULTS:Immediately after excision, perfusion increased in the wound edge and the peri-wound tissue, reaching approximately 157% of reference values (p < 0.01), reflecting immediate effects of surgery. At 1 week, perfusion increased further, likely driven by inflammation and angiogenesis (193%, p < 0.001). Perfusion gradually decreased at 6-8 weeks, aligning with active tissue remodeling, and continued to normalize at 4-5 months (123%, p > 0.05). By 12 months, perfusion returned to baseline levels, reflecting wound maturation (109%, p > 0.05). In cases with directing sutures, perfusion initially decreased to 64% at the wound edge, presumably due to tension-induced hypoperfusion, but returned to baseline after 6-8 weeks. CONCLUSION:This study highlights the critical role of blood perfusion in the healing of periocular defects treated with laissez-faire. The vascular network is preserved, enabling an immediate increase in perfusion, facilitating revascularization and wound healing. Further studies are needed to evaluate efficacy and long-term outcomes in comparison with reconstructive surgery.

Photoacoustic imaging can potentially map oxygen saturation (sO2) non-invasively. However, in-vivo human application is challenging due to spectral coloring, which causes a wavelength-dependent fluence attenuation and uncertainty in the estimation of chromophore concentrations deep in tissue. This study compares the performances of two previously proposed methods for spectral coloring compensation on in-vivo human data. Both methods have been modified and adapted to this context. The first modified method was evaluated using a tissuemimicking phantom, showing restoration of the original spectrum of the target and decreasing the relative mean square error from 65% to 1.2% for the highest concentration. Spatial maps of sO2 were estimated from in-vivo human finger measurements using both methods and compared with linear unmixing. Both methods reconstructed comparable values of sO2 and reduced depth-dependent changes in sO2, typically seen with linear unmixing, resulting in a gradient of saturation closer to zero as expected physiologically.

BACKGROUND:Large lower eyelid defects resulting from tumour removal are frequently reconstructed using a tarsoconjunctival flap from the upper eyelid together with an overlying free skin graft, the so-called Hughes procedure. One disadvantage of this technique is that the tarsoconjunctival flap occludes the eye during the revascularization of the graft, which is particularly troublesome for patients with poor vision in the other eye. Another alternative method for reconstructing large lower eyelid defects is the use of a free bilamellar eyelid graft with the advantage that it is a single-stage procedure and that the vision is not occluded during the healing process. However, both these methods require extensive surgery, which is time-consuming and might be too much effort for the frail and elderly. In these specific cases, where one wishes to avoid extensive surgery, laissez-faire treatment, so-called self-healing, might be an alternative. METHODS:46 patients undergoing laissez-faire treatment for periocular tumour defects were included. Surgical defects were in the medial canthal area (n = 10) and the lower eyelid (n = 28), with the latter classified as proportional (n = 21) or disproportional (n = 7) based on the anterior to posterior lamellae ratio. Cases requiring repeated surgical excisions due to tumour-positive margins (n = 8) were analysed separately. Wound contraction was assessed through serial photography after 1 week, 3 weeks, 6-8 weeks, and 5 months to 2 years. Defect size was standardized using corneal area measurements. RESULTS:Proportional lower eyelid defects exhibited predictable healing, with rapid wound contraction the first 6-8 weeks and minimal complications. Disproportional defects showed uneven healing, resulting in ectropion or significant tissue loss in 6 of 7 cases. Medial canthal defects generally healed well, but larger defects (>50% of corneal area) took longer to contract and were associated with traction-related complications in isolated cases. Repeated surgical excisions were associated with a higher prevalence of complications, including ectropion, entropion, and residual defects. CONCLUSIONS:Defect geometry is crucial in the healing process and clinical outcomes of periocular defects treated with laissez-faire. Medial canthal defects and proportional lower eyelid defects heal more reliably, while disproportional and large medial canthal defects, as well as cases requiring repeated surgical excisions, pose a higher risk of complications. These findings emphasize the importance of careful patient selection and defect analysis to optimize outcomes.

Introduction:Sentinel vessels provide an important early indication of underlying ocular neoplasm. To date, there is no noninvasive technique available for imaging and mapping of their vascular supply, which remains largely unstudied. We aimed to map sentinel vessels in uveal melanomas noninvasively by laser speckle contrast imaging (LSCI). Case Presentations:This report describes a case series of 4 patients undergoing enucleation due to uveal melanoma. Perfusion was imaged using LSCI during the successive detachment of the four rectus muscles, with their ciliary arteries, and the optic nerve with its ophthalmic artery. Tumor location and possible extrascleral growth were analyzed histopathologically. Sentinel vessels in uveal melanoma could be visualized noninvasively using LSCI, appearing broader and tortuous compared to surrounding vessels. The perfusion in the sentinel vessels was 24-94% higher than in the episcleral vessels. The origin of the sentinel vessel could be determined by perfusion monitoring during the successive detachment of the rectus muscles and the optic nerve. In 3 patients, the sentinel vessel was supplied by the anterior ciliary arteries and in 1 patient by the ophthalmic artery. In one of the cases, the sentinel vessel was not visible upon visual inspection. Conclusion:This is the first study of its kind demonstrating detailed mapping of sentinel vessels in uveal melanoma using LSCI. LSCI shows potential for the detection of sentinel vessels before they are visible in slit lamp examination. Vascular changes are a hallmark of tumor growth, and noninvasive imaging with LSCI may be a useful diagnostic tool for the detection of uveal melanoma.

PURPOSE:The gold standard for skin cancer diagnosis is surgical excisional biopsy and histopathological examination. Several non-invasive diagnostic techniques exist, although they have not yet translated into clinical use. This is a proof-of-concept study to assess the possibility of imaging an angiosarcoma in the periocular area. METHODS:We use laser speckle, hyperspectral, and photoacoustic imaging to monitor blood perfusion and oxygen saturation, as well as the molecular composition of the tissue. The information obtained from each imaging modality was combined in order to yield a more comprehensive picture of the function, as well as molecular composition of a rapidly growing cutaneous angiosarcoma in the periocular area. RESULTS:We found an increase in perfusion coupled with a reduction in oxygen saturation in the angiosarcoma. We could also extract the molecular composition of the angiosarcoma at a depth, depicting both the oxygen saturation and highlighting the presence of connective tissue via collagen. CONCLUSIONS:We demonstrate the different physiological parameters that can be obtained with the different techniques and how these can be combined to provide detailed 3D maps of the functional and molecular properties of tumors useful in preoperative assessment.

Objective. The availability of tissue-mimicking materials (TMMs) for manufacturing high-quality phantoms is crucial for standardization, evaluating novel quantitative approaches, and clinically translating new imaging modalities, such as photoacoustic imaging (PAI). Recently, a gel comprising the copolymer styrene-ethylene/butylene-styrene (SEBS) in mineral oil has shown significant potential as TMM due to its optical and acoustic properties akin to soft tissue. We propose using artists' oil-based inks dissolved and diluted in balsam turpentine to tune the optical properties.Approach. A TMM was fabricated by mixing a SEBS copolymer and mineral oil, supplemented with additives to tune its optical absorption and scattering properties independently. A systematic investigation of the tuning accuracies and relationships between concentrations of oil-based pigments and optical absorption properties of the TMM across visible and near-infrared wavelengths using collimated transmission spectroscopy was conducted. The photoacoustic spectrum of various oil-based inks was studied to analyze the effect of increasing concentration and depth.Main results. Artists' oil-based inks dissolved in turpentine proved effective as additives to tune the optical absorption properties of mineral oil SEBS-gel with high accuracy. The TMMs demonstrated long-term stability and suitability for producing phantoms with desired optical absorption properties for PAI studies.Significance. The findings, including tuning of optical absorption and spectral shape, suggest that this TMM facilitates the development of more sophisticated phantoms of arbitrary shapes. This approach holds promise for advancing the development of PAI, including investigation of the spectral coloring effect. In addition, it can potentially aid in the development and clinical translation of ultrasound optical tomography.

PURPOSE:The efficacy of cryosurgery is believed to depend on the thaw time. The presence of adrenaline in local anesthetics affects blood perfusion, and may thus also affect the thaw time. The aim of the present study was to use IR thermography to monitor the tissue temperature during cryosurgery of actinic keratosis, and to assess the effect of adrenaline in local anesthetics. METHODS:Twelve patients with actinic keratosis in the periorbital region underwent cryosurgery. The temperature was continuously mapped using a high-precision IR camera and was also visually assessed by the surgeon. The results obtained when employing local anesthetics with and without adrenaline were compared. RESULTS:The temperature change during thawing showed a triphasic pattern. The thaw time was significantly longer when using an anesthetic with adrenaline. This was observed with both IR thermography and by visual observation. CONCLUSIONS:The findings indicate that a longer freezing time may be needed when using a local anesthetic without adrenaline to achieve the same cryo-effect as when using a local anesthetic with adrenaline. A larger clinical trial is needed on the effects of using local anesthetics with and without adrenaline to treat actinic keratosis, for example, the clearance rate, before recommendations can be made concerning their use.

PurposeThere is a need for a simple, non-invasive, and easily accessible 3D imaging technique for the anophthalmic socket to create imaging data for future 3D printing of prostheses. This study aimed to investigate the feasibility of using a novel handheld tomographic ultrasound for 3D mapping of the anophthalmic socket.MethodsTen anophthalmic sockets were scanned using a tomographic ultrasound system and the results were compared to CT scanned impression molds from the same sockets.ResultsThe tomographic ultrasound provided detailed 3D maps of the anophthalmic sockets. The mean difference between the ultrasound-mapped socket and the CT-scanned imprints was within clinically acceptable limits for most patients. Specifically, the minimum separation distance was less than 3 mm in most cases. In three patients, larger deviations were noted as a result of uneven socket surfaces, indicating the need for further refinement in these cases.ConclusionsTomographic ultrasound shows promise for 3D imaging of the posterior surface of the anophthalmic socket and may, in the future, support 3D printing of prostheses. However, further refinement is needed to make the technique clinically applicable

In the dawning era of artificial intelligence (AI), health care stands to undergo a significant transformation with the increasing digitalization of patient data. Digital imaging, in particular, will serve as an important platform for AI to aid decision making and diagnostics. A growing number of studies demonstrate the potential of automatic pre-surgical skin tumor delineation, which could have tremendous impact on clinical practice. However, current methods rely on having ground truth images in which tumor borders are already identified, which is not clinically possible. We report a novel approach where hyperspectral images provide spectra from small regions representing healthy tissue and tumor, which are used to generate prediction maps using artificial neural networks (ANNs), after which a segmentation algorithm automatically identifies the tumor borders. This circumvents the need for ground truth images, since an ANN model is trained with data from each individual patient, representing a more clinically relevant approach.

PURPOSE:In oculoplastic surgery the eyelid tissue is frequently stretched in order to repair defects after tumor surgery. However, there is a paucity of research regarding how stretching affects eyelids. The purpose of this study was to gain insight into how traction force affects eyelid stretch as well as tissue perfusion, using a laser-based in vivo monitoring technique. METHOD:Lower-lid pentagonal resections were performed in eight patients and a total of nine eyelids. The medial section of the eyelid was then stretched using a dynamometer up to a force of 2.3 Newtons (N), and eyelid stretching and blood perfusion were continuously measured using laser speckle contrast imaging. RESULTS:Tissue perfusion decreased exponentially when eyelid tissue was stretched, with an initial sharp decline followed by a more gradual reduction. Perfusion approached zero at a force of approximately 2.0 N. The length of the eyelid increased with increasing force up to 1.5 N, after which there was only a very slight increase in length. CONCLUSIONS:Eyelid tissue seems to respond to traction in a non-linear fashion, where the initial force results in the greatest eyelid stretching and reduction in blood perfusion. The results provide information on the effects of a large force for direct closure of large eyelid defects. Considering how quickly perfusion approaches zero, the high success rate of eyelid reconstruction surgery is likely a testament to the extensive vascularization of the periocular region.

Clinical determination of oxygen saturation (sO2) in patients is commonly performed via non-invasive optical techniques. However, reliance on a few wavelengths and some form of pre-determined calibration introduces limits to how these methods can be used. One example involves the assessment of sO2 after injection of local anesthetic using epinephrine, where some controversy exists around the time it takes for the epinephrine to have an effect. This is likely caused by a change in the tissue environment not accounted for by standard calibrated instruments and conventional analysis techniques. The present study aims to account for this changing environment by acquiring absorption spectra using hyperspectral imaging (HSI) and diffuse reflectance spectroscopy (DRS) before, during, and after the injection of local anesthesia containing epinephrine in human volunteers. We demonstrate the need to account for multiple absorbing species when applying linear spectral unmixing in order to obtain more clinically relevant sO2 values. In particular, we demonstrate how the inclusion of water absorption greatly affects the rate at which sO2 seemingly drops, which in turn sheds light on the current debate regarding the time required for local anesthesia with epinephrine to have an effect. In general, this work provides important insight into how spectral analysis methods need to be adapted to specific clinical scenarios to more accurately assess sO2.

BACKGROUND:Anterior segment ischaemia (ASI) is a rare but feared complication associated with strabismus surgery, arising from damage of the anterior ciliary arteries that run along the extraocular rectus muscles. It has been reported that the risk of ASI following strabismus surgery increases when the vertical rectus muscles are involved. The aim of the present study was to monitor anterior segment perfusion in real time during inferior rectus muscle surgery. METHODS:17 eyes in 16 patients undergoing surgery on the inferior rectus muscle were included. Perfusion was measured in the adjacent paralimbal and iris tissue, before and after inferior rectus muscle detachment, using laser speckle contrast imaging. RESULTS:The paralimbal vascular network was clearly visualised in the perfusion images, whereas the signals from the iris were lower. Detachment of the inferior rectus muscle resulted in a reduction in paralimbal and iris perfusion by a median of 33% (p<0.0001) and 11% (p=0.0174), respectively. CONCLUSION:Strabismus surgery involving the inferior rectus muscle significantly affects perfusion to the anterior segment, and to a greater extent than previously observed following surgery on horizontal rectus muscles (where the decrease was only 23% and 5%).

OBJECTIVE:Conventional two-dimensional ultrasound has been assessed for the non-invasive diagnosis of giant cell arteritis (GCA), but the results are operator dependent, resulting in low sensitivity. Tomographic three-dimensional (3D) ultrasound is a novel technique that enables the objective documentation of vessel geometry. Here, for the first time, its utility is assessed for visualizing temporal arteries. METHOD:The temporal artery of 14 healthy subjects and three subjects with suspected GCA was examined using tomographic 3D ultrasound. RESULTS:This technique enabled 3D mapping of the architecture of the temporal artery. The inner and outer vessel diameters showed considerable interindividual variability. However, calculation of the vessel wall fraction revealed the combination of vessel wall thickening and lumen narrowing, which may be indicative of GCA. CONCLUSIONS:This proof-of-concept study indicates that tomographic 3D ultrasound can be used for objective mapping of the temporal artery. The technique must be evaluated regarding its diagnostic sensitivity in GCA before it can be introduced in clinical practice.