Pathergy-like reaction induced by laser hair removal in a patient with Behçet disease.

Behçet disease (BD) is a rare systemic vasculitis of unknown etiology, primarily characterized by recurrent oral aphthous ulcers, genital ulcers, uveitis, and skin lesions. Pathergy test positivity is a nonspecific inflammatory response of the skin to trauma and supports the diagnosis. Recently, new inducers of pathergy reactions have been identified, for example, the placement of dental braces and laser hair removal. Our clinical case highlights the importance of thinking about this potential pathergy inducer in BD patients, to improve their quality of life and avoid complications.

Extensive severe intraorbital arteriovenous malformations: report of a rare laser complication and successful management.

Arteriovenous malformations (AVMs) are rare congenital errors of vascular morphogenesis, characterised by abnormal direct communications between arteries and veins, bypassing the normal capillary bed. Apart from the central nervous system, typical locations include the head and neck, and less frequently limbs, trunk or internal organs. AVMs of the head and neck often become clinically evident and symptomatic only in later childhood and are characterised by a history of variable growth, sometimes leading to large, deforming, pulsating masses with a propensity to massive haemorrhage. Therapeutic strategy is based on selective embolisation, surgical excision, or a combination of both. Radical surgical excision of local AVMs is the only effective treatment but it may be mutilating, especially for AVMs of the head and neck. Laser therapy represents a good option to treat the cutaneous aspects of AVMs nevertheless, its efficacy is limited. To the date, pharmacological therapy for AVMs is still on debate due to its controversial outcomes as it seems not as effective as other treatments and usually requires a longer course of application. However, pharmacological therapy could be useful in selected patients and for AVMs nonresponsive to traditional treatment, allowing them to obtain acceptable results without serious complications. This paper reports the case of a serious laser complication of extensive intraorbital AVM successfully treated by local reconstruction and topical pharmacological treatment.

Comparison of the efficacy and safety of lasers, topical timolol, and combination therapy for the treatment of infantile hemangioma: A meta-analysis of 10 studies.

Topical timolol and lasers are widely used for the treatment of infantile hemangioma (IH), and they can replace propranolol as the first-line treatment of IH. We aimed to investigate the efficacy and safety of topical timolol alone or lasers plus topical timolol versus lasers alone for the treatment of IH using a meta-analysis. We searched the PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases. A more conservative random effect model meta-analysis technique was used to analyze the efficacy and adverse reactions of timolol and lasers. Ten RCTs with a total of 979 patients with IH were included in this meta-analysis. Treatment with topical timolol alone was as effective as lasers in treating IH (risk ratio [RR] = 0.99, p = 0.94), with similar adverse events. The difference was not statistically significant (RR = 1.67, p = 0.14). Combined treatment with topical timolol and lasers showed a favorable response rate compared with treatment with either lasers (RR = 1.23, p = 0.01) or topical timolol (RR = 1.35, p = 0.001) alone. Furthermore, compared to topical timolol alone, the combined treatment indicated similar risks of adverse events (RR = 0.70, p = 0.38) but fewer risks of adverse events (RR = 0.39, p = 0.004) compared to lasers alone. This meta-analysis provided evidences that a combined treatment with topical timolol and lasers might be more effective than a single treatment strategy in infants with IH, and with no significant increase in adverse reactions. The combination of topical timolol and laser therapy might be the preferred choice for the treatment of IHs.

Comparative transcriptome analysis of human and murine choroidal neovascularization identifies fibroblast growth factor inducible-14 as phylogenetically conserved mediator of neovascular age-related macular degeneration.

BACKGROUND: Visual outcome of patients with neovascular age-related macular degeneration has significantly improved during the last years following the introduction of anti-vascular endothelial growth factor (VEGF) therapy. However, about one third of patients show persistent exudation and decreasing visual acuity despite recurrent anti-VEGF treatment, which implies a role of other, still unknown proangiogenic mediators. METHODS: The present study applied transcriptional profiling of human and mouse (C57BL/6J wildtype) choroidal neovascularization (CNV) membranes each with reference to healthy control tissue to identify yet unrecognized mediators of CNV formation. Key factors were further investigated by immunohistochemistry as well as by intravitreal inhibition experiments and multiplex protein assays in the laser-induced CNV mouse model. FINDINGS: Transcriptional profiles of CNV membranes were characterized by enhanced activation of blood vessel development, cytoskeletal organization, and cytokine production, with angiogenesis and wound healing processes predominating in humans and activation of immune processes in mice. Besides several species-specific factors, 95 phylogenetically conserved CNV-associated genes were detected, among which fibroblast growth factor inducible-14 (FN14), a member of the tumor necrosis factor (TNF) receptor family, was identified as a key player of CNV formation. Blocking the pathway by intravitreal injection of a FN14 decoy receptor modulated the cytokine profile - most notably IL-6 - and led to a significant reduction of CNV size in vivo. INTERPRETATION: This study characterizes the transcriptome of human and mouse CNV membranes in an unprejudiced manner and identifies FN14 as a phylogenetically conserved mediator of CNV formation and a promising new therapeutic target for neovascular AMD. FUNDING: This study was funded by the Helmut Ecker Foundation and the Volker Homann Foundation.

SELF-INFLICTED LASER-INDUCED MACULOPATHY MASQUERADING AS POSTERIOR UVEITIS IN A PATIENT WITH SUSPECTED IgG4-RELATED DISEASE.

PURPOSE: To report the clinical presentation and imaging features in a case of bilateral self-inflicted handheld laser-induced maculopathy which masqueraded as progressive posterior uveitis in a patient with suspected IgG4-related disease. METHODS: Case report with clinical history, fundus photographs, fluorescein angiography, indocyanine green angiography, and swept-source optical coherence tomography. RESULTS: A young Asian Indian man presented with sudden progressive bilateral visual loss over the past 1 week. He was being treated with oral corticosteroids for multiple subcutaneous skin lesions believed to be due to IgG4-related disease. Findings included bilateral central areas of outer retinal disruption with eccentric linear and serpentine lesions showing hypoautofluorescence. Hyperreflective bands extending from the retinal pigment epithelium and interdigitation zone to the outer plexiform layer were present on swept-source optical coherence tomography. After careful history and evaluation of multimodal imaging, posterior uveitis was excluded, and a diagnosis of handheld laser-induced maculopathy was established. CONCLUSION: Pattern recognition is important in establishing a diagnosis of self-inflicted handheld laser-induced maculopathy which can masquerade as posterior uveitis. Increasing availability of powerful Class IIIb laser devices in both developed and developing countries will likely increase the incidence of this entity.

Immunosenescence in Choroidal Neovascularization (CNV)-Transcriptional Profiling of Naïve and CNV-Associated Retinal Myeloid Cells during Aging.

Immunosenescence is considered a possible factor in the development of age-related macular degeneration and choroidal neovascularization (CNV). However, age-related changes of myeloid cells (MCs), such as microglia and macrophages, in the healthy retina or during CNV formation are ill-defined. In this study, Cx3cr1-positive MCs were isolated by fluorescence-activated cell sorting from six-week (young) and two-year-old (old) Cx3cr1GFP/+ mice, both during physiological aging and laser-induced CNV development. High-throughput RNA-sequencing was performed to define the age-dependent transcriptional differences in MCs during physiological aging and CNV development, complemented by immunohistochemical characterization and the quantification of MCs, as well as CNV size measurements. These analyses revealed that myeloid cells change their transcriptional profile during both aging and CNV development. In the steady state, senescent MCs demonstrated an upregulation of factors contributing to cell proliferation and chemotaxis, such as Cxcl13 and Cxcl14, as well as the downregulation of microglial signature genes. During CNV formation, aged myeloid cells revealed a significant upregulation of angiogenic factors such as Arg1 and Lrg1 concomitant with significantly enlarged CNV and an increased accumulation of MCs in aged mice in comparison to young mice. Future studies need to clarify whether this observation is an epiphenomenon or a causal relationship to determine the role of immunosenescence in CNV formation.

Thermo-vibrational analyses of skin tissue subjected to laser heating source in thermal therapy.

Laser-induced thermal therapy, due to its applications in various clinical treatments, has become an efficient alternative, especially for skin ablation. In this work, the two-dimensional thermomechanical response of skin tissue subjected to different types of thermal loading is investigated. Considering the thermoelastic coupling term, the two-dimensional differential equation of heat conduction in the skin tissue based on the Cattaneo-Vernotte heat conduction law is presented. The two-dimensional differential equation of the tissue displacement coupled with the two-dimensional hyperbolic heat conduction equation in the tissue is solved simultaneously to analyze the thermal and mechanical response of the skin tissue. The existence of mixed complicated boundary conditions makes the problem so complex and intricate. The Galerkin-based reduced-order model has been utilized to solve the two-sided coupled differential equations of vibration and heat transfer in the tissue with accompanying complicated boundary conditions. The effect of various types of heating sources such as thermal shock, single and repetitive pulses, repeating sequence stairs, ramp-type, and harmonic-type heating, on the thermomechanical response of the tissue is investigated. The temperature distribution in the tissue along depth and radial direction is also presented. The transient temperature and displacement response of tissue considering different relaxation times are studied, and the results are discussed in detail.

Low-Energy Laser-Driven Ultrashort Pulsed Electron Beam Irradiation-Induced Immune Response in Rats.

The development of new laser-driven electron linear accelerators, providing unique ultrashort pulsed electron beams (UPEBs) with low repetition rates, opens new opportunities for radiotherapy and new fronts for radiobiological research in general. Considering the growing interest in the application of UPEBs in radiation biology and medicine, the aim of this study was to reveal the changes in immune system in response to low-energy laser-driven UPEB whole-body irradiation in rodents. Forty male albino Wistar rats were exposed to laser-driven UPEB irradiation, after which different immunological parameters were studied on the 1st, 3rd, 7th, 14th, and 28th day after irradiation. According to the results, this type of irradiation induces alterations in the rat immune system, particularly by increasing the production of pro- and anti-inflammatory cytokines and elevating the DNA damage rate. Moreover, such an immune response reaches its maximal levels on the third day after laser-driven UPEB whole-body irradiation, showing partial recovery on subsequent days with a total recovery on the 28th day. The results of this study provide valuable insight into the effect of laser-driven UPEB whole-body irradiation on the immune system of the animals and support further animal experiments on the role of this novel type of irradiation.

Zones of cellular damage around pulsed-laser wounds.

After a tissue is wounded, cells surrounding the wound adopt distinct wound-healing behaviors to repair the tissue. Considerable effort has been spent on understanding the signaling pathways that regulate immune and tissue-resident cells as they respond to wounds, but these signals must ultimately originate from the physical damage inflicted by the wound. Tissue wounds comprise several types of cellular damage, and recent work indicates that different types of cellular damage initiate different types of signaling. Hence to understand wound signaling, it is important to identify and localize the types of wound-induced cellular damage. Laser ablation is widely used by researchers to create reproducible, aseptic wounds in a tissue that can be live-imaged. Because laser wounding involves a combination of photochemical, photothermal and photomechanical mechanisms, each with distinct spatial dependencies, cells around a pulsed-laser wound will experience a gradient of damage. Here we exploit this gradient to create a map of wound-induced cellular damage. Using genetically-encoded fluorescent proteins, we monitor damaged cellular and sub-cellular components of epithelial cells in living Drosophila pupae in the seconds to minutes following wounding. We hypothesized that the regions of damage would be predictably arrayed around wounds of varying sizes, and subsequent analysis found that all damage radii are linearly related over a 3-fold range of wound size. Thus, around laser wounds, the distinct regions of damage can be estimated after measuring any one. This report identifies several different types of cellular damage within a wounded epithelial tissue in a living animal. By quantitatively mapping the size and placement of these different types of damage, we set the foundation for tracing wound-induced signaling back to the damage that initiates it.

Dendritic cells play no significant role in the laser-induced choroidal neovascularization model.

Age-related macular degeneration (AMD) is genetically associated with complement. Dendritic cells (DCs) play key roles during innate and adaptive immunity, and express complement components and their receptors. We investigated ocular DC heterogeneity and the role of DCs in the laser-induced choroidal neovascularization (CNV) model. In order to determine the function of DCs, we used two models of DC deficiency: the Flt3-/- and Flt3l-/- mouse. We identified three types of ocular DCs: plasmacytoid DC, classical DC-1, and classical DC-2. At steady-state, classical DCs were found in the iris and choroid but were not detectable in the retina. Plasmacytoid DCs existed at very low levels in iris, choroid, and retina. After laser injury, the number of each DC subset was up-regulated in the choroid and retina. In Flt3-/- mice, we found reduced numbers of classical DCs at steady-state, but each DC subset equally increased after laser injury between wildtype and Flt3-/- mice. In Flt3l-/- mice, each DC subsets was severely reduced after laser injury. Neither Flt3-/- or Flt3l-/- mice demonstrated reduced CNV area compared to wildtype mice. DCs do not play any significant role during the laser-induced CNV model of neovascular AMD.

Laser-Induced Apoptosis of Corticothalamic Neurons in Layer VI of Auditory Cortex Impact on Cortical Frequency Processing.

Corticofugal projections outnumber subcortical input projections by far. However, the specific role for signal processing of corticofugal feedback is still less well understood in comparisonto the feedforward projection. Here, we lesioned corticothalamic (CT) neurons in layers V and/or VI of the auditory cortex of Mongolian gerbils by laser-induced photolysis to investigate their contribution to cortical activation patterns. We have used laminar current-source density (CSD) recordings of tone-evoked responses and could show that, particularly, lesion of CT neurons in layer VI affected cortical frequency processing. Specifically, we found a decreased gain of best-frequency input in thalamocortical (TC)-recipient input layers that correlated with the relative lesion of layer VI neurons, but not layer V neurons. Using cortical silencing with the GABA a -agonist muscimol and layer-specific intracortical microstimulation (ICMS), we found that direct activation of infragranular layers recruited a local recurrent cortico-thalamo-cortical loop of synaptic input. This recurrent feedback was also only interrupted when lesioning layer VI neurons, but not cells in layer V. Our study thereby shows distinct roles of these two types of CT neurons suggesting a particular impact of CT feedback from layer VI to affect the local feedforward frequency processing in auditory cortex.

Electrosurgery or laser for benign prostatic enlargement: trumpcard or pitfalls.

PURPOSE OF REVIEW: To summarize and comment on publications of the last 2 years in the field of endoscopic surgery for benign prostatic enlargement, focusing on similarities and differences of laser and electrosurgery. RECENT FINDINGS: Because of good hemostasis and safety, invasive endoscopic surgery has evolved to a choice of treatment for vulnerable patients with ongoing antithrombotic medication and in same-day surgery. Recent publications show a good perioperative course and no deterioration in the postoperative outcome. Furthermore, alterations to the original surgical techniques of resection, enucleation, and vaporization have increased the preservation rate for antegrade ejaculation, advancing them to an appealing choice of treatment for sexually active men. Favorable outcomes can be achieved in both laser and electrosurgery. Only the choice of the surgical technique determines the outcome. SUMMARY: Various invasive endoscopic surgical techniques are available, offering different advantages and disadvantages for the patient. All of them can be performed with laser and electrosurgery. Therefore, focusing on the proper choice of surgical technique instead of the energy source will guarantee the patient to benefit most.

Effect of shock wave power spectrum on the inner ear pathophysiology in blast-induced hearing loss.

Blast exposure can induce various types of hearing impairment, including permanent hearing loss, tinnitus, and hyperacusis. Herein, we conducted a detailed investigation of the cochlear pathophysiology in blast-induced hearing loss in mice using two blasts with different characteristics: a low-frequency dominant blast generated by a shock tube and a high-frequency dominant shock wave generated by laser irradiation (laser-induced shock wave). The pattern of sensorineural hearing loss (SNHL) was low-frequency- and high-frequency-dominant in response to the low- and high-frequency blasts, respectively. Pathological examination revealed that cochlear synaptopathy was the most frequent cochlear pathology after blast exposure, which involved synapse loss in the inner hair cells without hair cell loss, depending on the power spectrum of the blast. This pathological change completely reflected the physiological analysis of wave I amplitude using auditory brainstem responses. Stereociliary bundle disruption in the outer hair cells was also dependent on the blast's power spectrum. Therefore, we demonstrated that the dominant frequency of the blast power spectrum was the principal factor determining the region of cochlear damage. We believe that the presenting models would be valuable both in blast research and the investigation of various types of hearing loss whose pathogenesis involves cochlear synaptopathy.

TPC2 promotes choroidal angiogenesis and inflammation in a mouse model of neovascular age-related macular degeneration.

Age-related macular degeneration (AMD) is the most common cause of blindness among the elderly and can be classified either as dry or as neovascular (or wet). Neovascular AMD is characterized by a strong immune response and the inadequate release of cytokines triggering angiogenesis and induction of photoreceptor death. The pathomechanisms of AMD are only partly understood. Here, we identify the endolysosomal two-pore cation channel TPC2 as a key factor of neovascularization and immune activation in the laser-induced choroidal neovascularization (CNV) mouse model of AMD. Block of TPC2 reduced retinal VEGFA and IL-1ß levels and diminished neovascularization and immune activation. Mechanistically, TPC2 mediates cationic currents in endolysosomal organelles of immune cells and lack of TPC2 leads to reduced IL-1ß levels in areas of choroidal neovascularization due to endolysosomal trapping. Taken together, our study identifies TPC2 as a promising novel therapeutic target for the treatment of AMD.

Effects of chiropractic spinal manipulation on laser-evoked pain and brain activity.

The aim of this study was to examine the mechanisms underlying hypoalgesia induced by spinal manipulation (SM). Eighty-two healthy volunteers were assigned to one of the four intervention groups: no intervention, SM at T4 (homosegmental to pain), SM at T8 (heterosegmental to pain) or light mechanical stimulus at T4 (placebo). Eighty laser stimuli were applied on back skin at T4 to evoke pain and brain activity related to Aδ- and C-fibers activation. The intervention was performed after 40 stimuli. Laser pain was decreased by SM at T4 (p = 0.028) but not T8 (p = 0.13), compared with placebo. However, brain activity related to Aδ-fibers activation was not significantly modulated (all p > 0.05), while C-fiber activity could not be measured reliably. This indicates that SM produces segmental hypoalgesia through inhibition of nociceptive processes that are independent of Aδ fibers. It remains to be clarified whether the effect is mediated by the inhibition of C-fiber activity.

Evaluation of laser induced sarcomere micro-damage: Role of damage extent and location in cardiomyocytes.

Whereas it is evident that a well aligned and regular sarcomeric structure in cardiomyocytes is vital for heart function, considerably less is known about the contribution of individual elements to the mechanics of the entire cell. For instance, it is unclear whether altered Z-disc elements are the reason or the outcome of related cardiomyopathies. Therefore, it is crucial to gain more insight into this cellular organization. This study utilizes femtosecond laser-based nanosurgery to better understand sarcomeres and their repair upon damage. We investigated the influence of the extent and the location of the Z-disc damage. A single, three, five or ten Z-disc ablations were performed in neonatal rat cardiomyocytes. We employed image-based analysis using a self-written software together with different already published algorithms. We observed that cardiomyocyte survival associated with the damage extent, but not with the cell area or the total number of Z-discs per cell. The cell survival is independent of the damage position and can be compensated. However, the sarcomere alignment/orientation is changing over time after ablation. The contraction time is also independent of the extent of damage for the tested parameters. Additionally, we observed shortening rates between 6-7% of the initial sarcomere length in laser treated cardiomyocytes. This rate is an important indicator for force generation in myocytes. In conclusion, femtosecond laser-based nanosurgery together with image-based sarcomere tracking is a powerful tool to better understand the Z-disc complex and its force propagation function and role in cellular mechanisms.

Endoscopic Repair of Type 1 Laryngeal Clefts and Deep Interarytenoid Notches: Cold Steel Versus Laser.

OBJECTIVES/HYPOTHESIS: Endoscopic repair is the preferred surgical treatment for type 1 laryngeal clefts (T1LCs) and deep interarytenoid notches (DINs). No studies exist showing differences in repair rates using laser and cold steel. Our objective is to assess overall success and revision rate for endoscopic cleft repair and determine whether there is any difference in surgical outcomes between cold steel and laser techniques. STUDY DESIGN: Retrospective chart review, cohort study. METHODS: Retrospective review at a quaternary care pediatric hospital. Included all patients who underwent endoscopic repair for T1LCs and DINs between January 2010 and December 2019. Demographics, comorbidities, surgical data, outcomes, and revision status were collected and analyzed. We excluded patients who did not have a follow-up at our institution. RESULTS: A total of 194 patients were identified, 14 were excluded for lack of follow-up data so 180 were analyzed. Of these, 127 had cold steel repair and 53 had laser repair. There is no significant difference in demographics or comorbidities. In the cold steel group, 4 of 127 (3.1%) had breakdown and in the laser group, 10 of 53 (18.9%) had breakdown. Patients who failed after a cold steel repair tended to break down later (median 12.7 months) when compared to laser repairs (median 2.1 months). Nine of the 10 patients with breakdown after laser repair were noted on initial postoperative evaluation. CONCLUSIONS: Endoscopic cleft repair is a well-described and effective method for repair of T1LCs and DINs. Both cold steel and laser have high success rates; however, higher failure rates were noted in the laser repair group. Failure after laser repair may occur earlier than failure after cold steel repair. But this did not reach significance. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:2805-2810, 2021.

Expression of purinergic receptors on microglia in the animal model of choroidal neovascularisation.

To investigate the effect of P2 receptor on microglia and its inhibitor PPADS on choroidal neovascularization. Forty CX3CR1GFP/+ mice were randomly divided into 8 groups. In addition to the normal group, the rest of groups were receiving laser treatment. The retina and choroid from the second, third, fourth and fifth group of mice were taken in the 1, 4, 7, 14 days after laser treatment. The mice in the sixth and seventh group received intravitreal injection of 2 µl PPADS or PBS respectively immediately after laser treatment. The mice in the eighth group received topical application of PPADS once per day of three days. The mice in sixth, seventh and eighth group received AF and FFA examination on the fourth day after laser treatment. Immunofluorescence histochemical staining and real-time quantitative PCR were used to evaluate P2 expression and its effect on choroidal neovascularization. After laser treatment, activated microglia can express P2 receptors (P2X4, P2X7, P2Y2 and P2Y12). The expression of P2 increased on the first day after laser damage, peaked on the fourth day (tP2X4 = 6.05, tP2X7 = 2.95, tP2Y2 = 3.67, tP2Y12 = 5.98, all P < 0.01), and then decreased. After PPADS inhibition, compared with the PBS injection group, the mRNA of P2X4, P2X7, P2Y2 and P2Y12 were decreased significantly in the PPADS injection group (tP2X4 = 5.54, tP2X7 = 9.82, tP2Y2 = 3.86, tP2Y12 = 7.91, all P < 0.01) and the PPADS topical application group (tP2X4 = 3.24, tP2X7 = 5.89, tP2Y2 = 6.75, tP2Y12 = 4.97, all P < 0.01). Compared with the PBS injection group, not only the activity of microglia cells but also the leakage of CNV decreased significantly (P < 0.01) in the PPADS injection group and the PPADS topical application group. But between two PPADS groups, the leakage of CNV had no difference (P = 0.864). After laser induced CNV, activated microglia can express P2 receptors. The P2 receptor inhibitor, PPADS, can significantly affect the function of microglia and inhibit the formation of choroidal neovascularization.

Quantum-enhanced nonlinear microscopy.

The performance of light microscopes is limited by the stochastic nature of light, which exists in discrete packets of energy known as photons. Randomness in the times that photons are detected introduces shot noise, which fundamentally constrains sensitivity, resolution and speed1. Although the long-established solution to this problem is to increase the intensity of the illumination light, this is not always possible when investigating living systems, because bright lasers can severely disturb biological processes2-4. Theory predicts that biological imaging may be improved without increasing light intensity by using quantum photon correlations1,5. Here we experimentally show that quantum correlations allow a signal-to-noise ratio beyond the photodamage limit of conventional microscopy. Our microscope is a coherent Raman microscope that offers subwavelength resolution and incorporates bright quantum correlated illumination. The correlations allow imaging of molecular bonds within a cell with a 35 per cent improved signal-to-noise ratio compared with conventional microscopy, corresponding to a 14 per cent improvement in concentration sensitivity. This enables the observation of biological structures that would not otherwise be resolved. Coherent Raman microscopes allow highly selective biomolecular fingerprinting in unlabelled specimens6,7, but photodamage is a major roadblock for many applications8,9. By showing that the photodamage limit can be overcome, our work will enable order-of-magnitude improvements in the signal-to-noise ratio and the imaging speed.