Cost-effectiveness of agents used for evaluation of ureteral patency during intraoperative cystoscopy in gynecologic and urogynecologic surgery.

BACKGROUND: Intraoperative evaluation of ureteral patency is often performed in gynecologic and urogynecologic surgery. Many agents are used to help assess the patency, each with its own associated cost, ease of use, and adverse reactions. Some agents, such as dextrose, are used as an instillation fluid to create a viscosity difference and aid the visualization of a ureteral jet. Others, such as oral phenazopyridine or the intravenous use of sodium fluorescein and indigo carmine, cause a color change of the urine to directly aid the visualization of ureteral jets. Recently, numerous studies have examined the efficacy and surgeon satisfaction of these agents. The studies have also emphasized certain options as associated with a lower cost. However, there have not been any cost studies comparing these agents. OBJECTIVE: To compare the cost-effectiveness of the following 4 agents that are commonly used in assessing ureteral patency intraoperatively: oral phenazopyridine, dextrose instillation, intravenous sodium fluorescein, and intravenous indigo carmine. STUDY DESIGN: We constructed a decision-analytic model to compare cystoscopy using oral phenazopyridine, dextrose instillation, intravenous sodium fluorescein, and intravenous indigo carmine. Failure to see efflux resulted in work-ups for ureteral obstruction. The probabilities were obtained from published studies, and the probability of successfully seeing efflux ranged from 0.92 with oral phenazopyridine to 0.99 with intravenous indigo carmine. The costs of the agents, adverse effects, and ureteral obstruction work-ups were obtained from the University of North Carolina at Chapel Hill Department of Pharmacy, the Healthcare Cost and Utilization Project 2016 database and the FAIR Health Consumer database. The cost of a ureteral obstruction work-up used in our model ranged from $9755 for intraoperative evaluation with retrograde pyelograms and stents to $29,034 for hospitalization. Our primary outcome was the incremental cost-effectiveness ratio per unnecessary work-up for ureteral obstruction avoided. Sensitivity analyses were performed to identify the key uncertainties. RESULTS: Oral phenazopyridine, followed by an intravenous agent if needed, had a mean cost of $110 per patient. Dextrose averaged $151 more per patient, with only a slight improvement in avoiding unnecessary ureteral obstruction work-ups and a higher cost associated with adverse reactions (incremental cost-effectiveness ratio, $62,000). Intravenous agents cost approximately $1000 more per patient and were less effective at preventing unnecessary work-ups. Sensitivity analyses did not identify any thresholds that would significantly change the outcomes. CONCLUSION: Our model suggests that oral phenazopyridine and dextrose instillation are the least expensive and the most effective agents to aid in the visualization of ureteral patency during intraoperative cystoscopy, although dextrose is associated with higher costs owing to a higher rate of adverse reactions (primarily urinary tract infections). Intravenous sodium fluorescein and indigo carmine are historically popular first-choice agents. However, they were found to be more expensive and less effective as primary agents in our model and should likely be reserved for use as secondary agents in the event that the visualization of ureteral jets is unclear with the initial use of phenazopyridine or dextrose.

Enhancement of Skin Permeation of a Hydrophilic Drug from Acryl-Based Pressure-Sensitive Adhesive Tape.

PURPOSE: Penetration enhancers are necessary to overcome a formidable barrier function of the stratum corneum in the development of topical formulations. Recently, non-lamella liquid crystal (NLLC)-forming lipids such as glycerol monooleate and phytantriol (PHY) are gaining increasing attention as a novel skin permeation enhancer. In the present study, fluorescein sodium (FL-Na) was used as a model hydrophilic drug, and acryl-base pressure-sensitive adhesive (PSA) tape containing NLLC forming lipids, mono-O-(5,9,13-trimethyl-4-tetradecenyl) glycerol ester (MGE) or PHY, was prepared to enhance drug permeation through the skin. METHODS: A PSA patch containing FL-Na was prepared by mixing FL-Na entrapped in NLLC and acrylic polymer. FL permeation through excised hairless rat skin, and also human skin, was investigated. Changes in lipid structure, folding/unfolding state of keratin in the stratum corneum, and penetration of MGE into the stratum corneum were investigated using confocal Raman microscopy. RESULTS: Enhanced FL permeation was observed by the application of a PSA patch containing MGE and PHY. Especially, dramatically enhancement effect was confirmed by 15% of MGE contained formulation. Penetration of MGE provided diminished orthorhombic crystal structure and a peak shift of the aliphatic CH3 vibration of keratin chains toward lower wavenumbers. CONCLUSION: The present results suggested that the formulation development by adding MGE may be useful for improving the skin permeation of mal-permeable drugs such as hydrophilic drugs.

Clinical comparison of tear film breakup time measurements in normal dogs using three different methods of fluorescein solution administration.

OBJECTIVE: To evaluate whether the method of fluorescein administration affects the results of tear film breakup time (TFBUT) measurement in normal dogs. ANIMALS STUDIED: Thirty-seven client and hospital staff owned dogs over 1 year of age with no known comorbidities or administration of systemic or topical ophthalmic medications. PROCEDURES: A prospective randomized three-way crossover study was conducted. All dogs received an abbreviated ophthalmic examination to rule out ocular surface disease. Using a 30-min washout interval period, each dog's right eye was received: (a) direct application of fluorescein stain strip with one drop of sterile eyewash, (b) direct application of fluorescein stain strip with two drops of sterile eyewash, or (c) application of one drop from a premade fluorescein solution (dilution of one strip in 0.3 mL sterile eyewash). Eyes were assessed using the cobalt blue filter of a slit lamp biomicroscope. TFBUT measurements were summarized as means ± standard deviation. The methods were compared using mixed model analysis of variance. All analyses were performed using sas version 9.4. RESULTS: Thirty-seven dogs met the inclusion criteria. Mean TFBUT ± standard deviation (SD) for the three described methods were: (a) 16.58s ± 6.9, (b) 15.98s ± 7.1, and (c) 16.43s ± 8.1. No differences between fluorescein stain application techniques were observed (p = .92). CONCLUSION: The technique of fluorescein solution administration did not affect TFBUT measurement in this population of healthy dogs.

Functional, structural, and molecular identification of lymphatic outflow from subconjunctival blebs.

The purpose of this study is to evaluate outflow pathways from subconjunctival blebs and to identify their identity. Post-mortem porcine (n = 20), human (n = 1), and bovine (n = 1) eyes were acquired, and tracers (fluorescein, indocyanine green, or fixable/fluorescent dextrans) were injected into the subconjunctival space to create raised blebs where outflow pathways were visualized qualitatively and quantitatively. Rodents with fluorescent reporter transgenes were imaged for structural comparison. Concurrent optical coherence tomography (OCT) was obtained to study the structural nature of these pathways. Using fixable/fluorescent dextrans, tracers were trapped to the bleb outflow pathway lumen walls for histological visualization and molecular identification using immunofluorescence against lymphatic and blood vessel markers. Bleb outflow pathways could be observed using all tracers in all species. Quantitative analysis showed that the nasal quadrant had more bleb-related outflow pathways compared to the temporal quadrant (nasal: 1.9±0.3 pathways vs. temporal: 0.7±0.2 pathways; p = 0.003). However, not all blebs resulted in an outflow pathway (0-pathways = 18.2%; 1-pathway = 36.4%; 2-pathways = 38.6%; and 3-pathways = 6.8%). Outflow signal was validated as true luminal pathways using optical coherence tomography and histology. Bicuspid valves were identified in the direction of flow in porcine eyes. Immunofluorescence of labeled pathways demonstrated a lymphatic (Prox-1 and podoplanin) but not a blood vessel (CD31) identity. Therefore, subconjunctival bleb outflow occurs in discrete luminal pathways. They are lymphatic as assessed by structural identification of valves and molecular identification of lymphatic markers. Better understanding of lymphatic outflow may lead to improved eye care for glaucoma surgery and ocular drug delivery.

Correlations Between Skin Barrier Integrity and Delivery of Hydrophilic Molecules in the Presence of Penetration Enhancers.

PURPOSE: We investigated the potential correlations between skin barrier integrity and hydrophilic drugs distribution in skin in the presence of different types of penetration enhancers (PEs) and their combinations. METHODS: We measured skin conductivity to evaluate skin barrier integrity before and after the topical application of different chemical PEs, physical PE, peptide PE and their combinations in vitro. We also investigated their effect on the skin distribution profiles of two hydrophilic model drugs, Fluorescein sodium (376 Da) and Fluorescein isothiocyanate-dextrans 10 (10 KDa). RESULTS: The physical PE significantly increased the skin conductivity compared to all other PEs, while the peptide PE had no effect on it. The drug deposition in different skin layers was not only dependent on PE applied but also its own molecular weight. We further found two excellent correlations: one (R2 = 0.9388) between skin barrier integrity and total skin absorption of FNa and another one(R2 = 0.9212) between skin barrier integrity and the deposition of FNa in dermis and receptor in presence of chemical or physical PEs and their combinations. CONCLUSIONS: The total skin absorption or the deposition in dermis and receptor of small hydrophilic drug in the presence of chemical and physical PEs and their combinations show a good correlation with skin barrier integrity. However, such correlations hold true neither for large hydrophilic drug nor for peptide PE. All good relationships found in this work will allow screening suitable PEs or combinations by measuring the skin conductivity induced by corresponding PEs. Graphical Abstract The total skin absorption of small hydrophilic drug shows a good correlation with skin barrier integrity in the presence of chemical and physical penetration enhancers and their combinations. However, such a correlation hold true neither for large hydrophilic drug nor for peptide penetration enhancer.

ULTRA-WIDE-FIELD IMAGING AND INTRAVENOUS FUNDUS FLUORESCEIN ANGIOGRAPHY IN INFANTS WITH RETINOPATHY OF PREMATURITY.

PURPOSE: To determine the feasibility of ultra-wide-field imaging and ultra-wide-field intravenous fundus fluorescein angiography (UWF-IV-FFA) in infants with retinopathy of prematurity (ROP) using Optos 200Tx. METHODS: We performed Optos 200Tx capturing on 32 premature infants (14 females) and UWF-IV-FFA with Optos 200Tx on 12 of the 32 infants between April 2017 and July 2018 at the affiliated eye hospital of Wenzhou Medical University and analyzed their fundus images. RESULTS: Ultra-wide-field color images were acquired from 32 infants (64 eyes). UWF-IV-FFA was performed successfully in 12 premature infants (24 eyes). No adverse events were observed. The ultra-wide-field Optos 200Tx color images and UWF-IV-FFA images revealed Stages 1, 2, and 3 ROP and aggressive posterior ROP. CONCLUSION: Ultra-wide-field imaging and intravenous fundus fluorescein angiography using Optos 200Tx are feasible in infants with ROP, which have the potential to screen, diagnose, and follow-up for ROP.

Case report of conjunctival sac fistula after cosmetic lateral canthoplasty.

BACKGROUND: To report a case of conjunctival sac fistula after cosmetic lateral canthoplasty which is rare. CASE PRESENTATION: A young women who underwent bilateral canthoplasty appeared with lacrimation of the right eye. We found there was a skin fistula with transparent tears at 2 mm lateral to the right canthus ligament and the liquid containing fluorescein was seen to overflow at the fistula after using fluorescein sodium eye drops. The number 7 lacrimal duct probe was visible under the temporal conjunctiva when exploring the fistula, and the fistula was about 4 mm. The patient was diagnosed with conjunctival sac fistula and fistula excision was performed. The patient did not tear abnormally after observation 3 months later and the incision healed well. CONCLUSIONS: The case report illustrates an uncommon post-lateral canthoplasty complication. We suggested that surgeons who perform this kind of surgery should ask about epiphora and look for conjunctival sac fistula at follow-up assessment.

Effects of radiation therapy on the meibomian glands and dry eye in patients with ocular adnexal mucosa-associated lymphoid tissue lymphoma.

BACKGROUND: Radiation therapy (RT) is the treatment of choice in patients with low-grade ocular adenexal mucosa-associated lymphoid tissue lymphoma (OAML) and many of them experience post-RT dry eye with varying severity. The purpose of the present study was to investigate ocular effects of RT on meibomian glands and dry eye by directly visualizing structural changes. Secondly, we focused on the comparison of two groups of patients according to tumor location and radiation technique. METHODS: Sixty-four eyes with OAML of conjunctiva, orbit, lacrimal gland, or lacrimal sac were grouped into conjunctival lymphoma and "orbital-type" lymphoma (i.e., orbit, lacrimal gland, and lacrimal sac). Subjects were investigated for morphological changes in meibomian glands by meiboscore grading system. Radiation technique was examined and Ocular Surface Disease Index (OSDI) questionnaire, Schirmer's test, tear film break-up time (TBUT), slit lamp examination of corneal surface and lid margin abnormality were conducted before and after RT. RESULTS: The increase in meiboscore was statistically significant over time after RT in both groups (P < 0.001). The extent of increase in meiboscore was significantly greater in the "orbital-type" lymphoma group than in the conjunctival lymphoma group (P < 0.001). The changes in OSDI, TBUT, corneal fluorescein staining score and lid margin abnormality score after RT were significantly different across two groups (P = 0.042, 0.001, 0.035 and 0.001, respectively). Schirmer's value decreased after RT in both groups. Dry eye symptoms were most severe right after RT in both groups, but a gradual resolution was noted in most patients with conjunctival lymphoma, whereas symptoms persisted in "orbital-type" lymphoma patients. The OSDI score and corneal fluorescein staining score were positively correlated with meiboscore in "orbital-type" patients at post-RT 6 months (r = 0.43, P = 0.04; r = 0.39, P = 0.03, respectively). CONCLUSIONS: Patients with OAML had different degrees of morphological changes in meibomian glands according to tumor location and radiation technique. "Orbital-type" lymphoma patients are more likely to experience severe injury to meibomian glands, which eventually leads to persistent dry eye. Patients with "orbital-type" lymphoma should be well informed of post-RT damage on meibomian glands and persistent dry eye.

Subjective and Objective Evaluation of the Effect of Blink Type on Tear-film Breakup Time and Its Estimation.

SIGNIFICANCE: While evaluating the tear-film breakup time, a careful set of precise instructions should be given to the subjects regarding the blink type because it substantially impacts the assessment of tear-film surface quality. PURPOSE: The purpose of this study was to determine to what extent the type of blink affects the tear-film breakup time and its assessment using two types of videokeratoscopes and the fluorescein test. METHODS: Thirty-three volunteers were assessed considering two different types of blinks: natural (short) and forced (unnaturally prolonged). Objective noninvasive breakup time estimation was performed using Oculus Keratograph 5M and Medmont E300, both equipped with tear-film analysis modules, followed by the fluorescein test. In addition, while overviewing videokeratoscopy recordings, noninvasive breakup time was assessed subjectively by one experienced observer marking the first noticeable distortion in the Placido-disk pattern. Statistical analyses included two-way ANOVA and paired-sample t test. The agreement between blinking and measuring modalities was assessed using Bland-Altman plots. RESULTS: Forced blink significantly shortened the tear-film breakup time in all measuring modalities (two-way ANOVA, P = .003). The mean difference between breakup time after natural and forced blink was 3.2 (P = .002), 2.4 (P = .005), and 2.1 seconds (P = .002), for Keratograph 5M, E300, and fluorescein test, respectively. The group median of differences between objective and subjective noninvasive breakup time was less than 1 second with both videokeratoscopes. The objective noninvasive breakup time measured with Keratograph 5M was significantly longer than those with E300 and fluorescein test (both P < .001). No statistically significant difference was found between E300 objective assessment and fluorescein test (P = .19). CONCLUSIONS: Forced blinks affect the assessment of tear-film stability. Hence, attention should be given in instructing the subjects before tear-film breakup time evaluation irrespectively to the method of measurement.

Dry Eye Disease Practice in Ghana: Diagnostic Perspectives, Treatment Modalities, and Challenges.

SIGNIFICANCE: There is a dearth of studies investigating the challenges encountered in dry eye practice. Profiling these barriers is crucial to improving dry eye diagnosis and patient care. PURPOSE: This study aimed to examine the diagnostic and treatment perspectives, and challenges in dry eye practice in Ghana. METHODS: An anonymous paper-based or web survey regarding dry eye practice pattern, practice challenges, and access to diagnostic tools was distributed to 280 potential participants. RESULTS: One hundred thirteen respondents completed the survey. Case history (92.5%), fluorescein tear breakup time (87.5%), and corneal fluorescein staining (72.5%) were the topmost procedures used for dry eye diagnosis. A preserved lubricant drop was the most commonly prescribed treatment of mild, moderate, and severe dry eye at the rates of 77.0, 83.2, and 77.0%, respectively. A few respondents prescribed cyclosporine (2.7%) or punctal plugs (5.3%) across all disease severities, and none used scleral lens, autologous serum tears, or thermal pulsation. Graduate professional training influenced the practice pattern of 82.3% of respondents, whereas continuing professional education influenced less than 1%. Approximately 70.1 and 92.8% of optometrists considered referring dry eye in children and cases that are unresponsive to treatment, respectively. Eighty-eight percent of practitioners indicated they experience a challenge in dry eye practice, with limited access to diagnostic tools (77.9%) and limited availability of effective dry eye medication on the Ghanaian market (50.4%) being the most frequent challenges. More than 85% of respondents had access to a fluorescein dye or slit-lamp biomicroscope; however, none had access to a phenol red thread, lissamine green dye, osmolarity technology, or meibography device. CONCLUSIONS: Practitioners' limited access to diagnostic tools/techniques and the limited effective dry eye treatments are major challenges encountered in dry eye practice in Ghana. Addressing these will improve dry eye practice and treatment outcomes in the country.

Topical intranasal fluorescein to localize a cerebrospinal fluid leak: a demonstration.

BACKGROUND: Intrathecal fluorescein is commonly used to localize cerebrospinal fluid leaks. This technique is invasive and associated with several potential adverse effects. The purpose of this video presentation is to demonstrate an alternative technique, the intranasal use of dilute topical fluorescein, to localize a cerebrospinal fluid leak intraoperatively. METHODS: A 45-year-old male with a history of benign intracranial hypertension and 2 months of right-sided rhinorrhea underwent surgical repair of a cerebrospinal fluid leak. Topical fluorescein was applied intraoperatively to localize the defect. RESULTS: At 1- and 3-month follow-ups the patient was without cerebrospinal fluid rhinorrhea and the middle turbinate flap was intact. CONCLUSION: Topical application of dilute intranasal fluorescein is a feasible and efficient tool for localizing cerebrospinal fluid leaks.

Is topical fluorescein that effective in endoscopic CSF leak closure?

PURPOSE: Several diagnostic modalities are used to detect CSF leaks. Intraoperative use of intrathecal fluorescein can help to detect and localize a CSF leak simultaneously. However, it is not FDA approved, the application is invasive and has serious complications. Topical fluorescein is reported to be a safe and sensitive alternative to ITF. In this study, we aimed to evaluate the effectiveness of topical fluorescein in CSF leak closure. METHODS: This retrospective study includes 27 consecutive patients (19 women, 8 men) who underwent endoscopic endonasal CSF leak closure using topical fluorescein, between 2011 and 2017. RESULTS: In two patients, radiologic studies false positively locate the defect. ß2 transferrin and topical fluorescein tests were positive in these patients. Both cases needed a second operation. CONCLUSION: If radiologic studies fail to locate the defect properly, topical fluorescein only confirms the CSF leak, but the defect cannot be located anatomically intraoperatively.

Antimicrobial activity of topical dyes used in clinical veterinary ophthalmology.

OBJECTIVE: To evaluate in vitro the antibacterial effects of fluorescein, rose bengal, and lissamine green topical ophthalmic dyes against selected Gram-positive and Gram-negative bacteria, and to evaluate whether preserved or preservative-free fluorescein solutions are able to inhibit or potentiate bacterial growth. PROCEDURES: Susceptibility testing was performed using the Kirby-Bauer disk diffusion method plated with clinical ocular isolates of Staphylococcus aureus, Staphylococcus pseudintermedius, Streptococcus spp., Escherichia coli, and Pseudomonas aeruginosa. Bacterial growth inhibition was evaluated 24 hours following the addition of commercially available fluorescein, rose bengal, and lissamine green sterile strips. Antimicrobial effectiveness testing was performed by inoculation of compounded 1% dye solutions, both with and without preservatives (fluorescein and lissamine contained thiomersal, and rose bengal contained nipagin and nepazol), with the five previously mentioned bacteria. Growth was evaluated at days 7, 14, and 28. RESULTS: All dyes showed antibacterial activity against Gram-positive organisms. Preservative-free compounded 1% fluorescein solution inhibited growth of Gram-positive organisms but not of Gram-negative organisms. Preservative-free rose bengal and lissamine green inhibited growth of both types of organisms. CONCLUSIONS: Preferably, ocular surface samples for antimicrobial culture should be taken prior to the administration of topical dyes, due to their potential antibacterial activity, particularly if undiluted strips are applied directly or commercial fluorescein solutions are used and not immediately rinsed. Ophthalmic dye solutions containing preservative are safe from bacterial growth for up to 28 days if properly handled and stored. The use of preservative-free fluorescein solutions should be avoided and preservative-free rose bengal and lissamine green should be handled carefully.

An [18F]-Positron Emitting Fluorophore Allows Safe Evaluation of Small Molecule Distribution in the CSF, CSF Fistulas, and CNS Device Placement.

The small molecule fluorescein is commonly used to guide the repair of cerebral spinal fluid leaks (CSFLs) in the clinic. We modified fluorescein so that it is also visible by positron emission tomography (PET). This probe was used to quantitatively track the fast distribution of small molecules in the CSF of rats. We tested this probe in models relevant to the clinical diagnosis and treatment of central nervous system (CNS) diseases that affect CSF flow. In this study, fluorescein was radiolabeled with fluorine-18 to produce Fc-AMBF3. [18/19F]-Fc-AMBF3 was introduced at trace quantities (13.2 nmols, 100 µCi) intrathecally (between L5 and L6) in rats to observe the dynamic distribution and clearance of small molecules in the CSF by both [18F]-PET and fluorescence (FL) imaging. Murine models were used to demonstrate the following utilities of Fc-AMBF3: (1) utility in monitoring the spontaneous CSFL repair of a compression fracture of the cribriform plate and (2) utility in quantifying CSF flow velocity during neurosurgical lumboperitoneal shunt placement. Fc-AMBF3 clearly delineated CSF-containing volumes based on noninvasive PET imaging and in ex vivo FL histology. In vivo morbidity (n = 16 rats, <2.7 mg/kg, 77 times the PET dose) was not observed. The clearance of the contrast agent from the CNS was rapid and quantitative (t1/2 = 33.8 ± 0.6 min by FL and t1/2 = 26.0 ± 0.5 min by PET). Fc-AMBF3 was cleared from the CSF through the vasculature and/or lymphatic system that supplies the cribriform plate and the temporal bone. Fc-AMBF3 can be used to diagnose CSFLs, image CSFL repair, and determine the CSF flow velocity in the CNS or through lumboperitoneal shunts by PET/FL imaging. In conclusion, Fc-AMBF3 PET imaging has been demonstrated to safely and dynamically quantitate CSF flow, diagnose fistulas associated with the CSF space, and approximate the clearance of small molecules in the CSF.

The ablative fractional coagulation zone influences skin fluorescence intensities of topically applied test molecules-An in vitro study with fluorescence microscopy and fluorescence confocal microscopy.

BACKGROUND: Ablative fractional laser (AFL) increases uptake of topically applied skin agents. The coagulation zone (CZ) surrounding vertically ablated channels may influence uptake of drugs. OBJECTIVES: To investigate impact of CZ thickness on skin fluorescence intensities (FI) of a hydrophilic molecule by means of fluorescence microscopy (FM) and fluorescence confocal microscopy (FCM). Second, to compare FI of hydrophilic and lipophilic test molecules by FCM. STUDY DESIGN/METHODS AND MATERIALS: Microchannels with CZ thicknesses of 0, 20, and 80 µm were generated by microneedles or AFL (10,600 nm). Channels were 700 µm deep and number of channels kept constant per skin area. After 4 hours of incubation, FI induced by sodium fluorescein (NAF, hydrophilic, logarithmic partition-coefficient (logP) = -1.52, MW = 376.26) were quantified in both CZ and surrounding skin by FM (0-1,500 µm) and FCM (0-90 µm). FI of NAF and carboxyfluorescein (CAF, lipophilic, logP = 2.9, MW = 376.32) were compared by FCM. RESULTS: By FM, NAF-induced FI were higher in CZ than in surrounding skin (P ≤ 0.001). Highest NAF-FI were induced in skin pretreated with a thin CZ (CZ-20 µm), assessed by both FM and FCM and in particular, FI were higher than in skin pretreated with no CZ (CZ-0 µm) (FM P ≤ 0.041, FCM P < 0.012). Skin FI remained constant to a depth of 500 µm, which corresponded to approximate depth of microchannels (CZ-0 µm, CZ-20 µm, CZ-80 µm: 0-500 µm P ≥ 0.107). In accordance with FM data, FCM showed higher FI within CZ than in surrounding skin, but gradually decreased to zero at a depth of 90 µm. NAF-FI were higher than CAF-FI (P ≤ 0.036), and highest CAF-FI were induced by CZ-0 µm and CZ-20 µm compared to CZ-80 µm (P ≤ 0.009). CONCLUSIONS: The influence of the CZ thickness on skin FI differs between small hydrophilic and lipophilic test molecules. Results may have clinical relevance for laser-assisted drug delivery. Lasers Surg. Med. 51:68-78, 2019. © 2018 Wiley Periodicals, Inc.

Fluorescein-assisted stereotactic needle biopsy of brain tumors: a single-center experience and systematic review.

Over the last years, fluorescence-based technology has begun an emergent intraoperative method for diagnostic confirmation of brain tumor tissue in stereotactic needle biopsy. However, the actual level of evidence is quite low, especially about fluorescein sodium (FL) application. This method needs to be further validated and better analyzed about its impact in clinical practice. Retrospective analysis of 11 cases with contrast-enhancing brain tumors, underwent awake stereotactic needle biopsy with intraoperative FL assistance (group 1), was verified under the operative microscope filter. This group was matched with a control group of 18 patients (group 2). In addition, a systematic literature review was performed in PubMed/Medline database according to PRISMA statement. All studies concerning FL or 5-ALA application in stereotactic biopsy as intraoperative confirmation of brain tumor tissue were included. The primary endpoint was the evaluation of diagnostic accuracy. In group 1, all fluorescent specimens were diagnostic. The number of samplings was the useful minimum and non-use of intraoperative neuropathological examination allowed to significantly reduce procedure time (42.09 vs 69.72 min of group 2). No complications occurred, and the average hospitalization time after procedure was 1.09 days (vs 2.33 of group 2). Literature analysis supports the usefulness of photodiagnosis and its high diagnostic yield especially at the core of high-grade/contrast-enhancing tumors. FL assistance during stereotactic biopsy of contrast-enhancing brain tumors may give a real-time confirmation of tumor tissue, maximizing the diagnostic yield, and reducing time of procedure, morbidity, and hospitalization.

A Novel Method for Rapid Bedside Measurement of GFR.

Background Direct quantitative measurement of GFR (mGFR) remains a specialized task primarily performed in research settings. Multiple formulas for estimating GFR have been developed that use the readily available endogenous biomarkers creatinine and/or cystatin C. However, eGFR formulas have limitations, and an accurate mGFR is necessary in some clinical situations and for certain patient populations. We conducted a prospective, open-label study to evaluate a novel rapid technique for determining plasma volume and mGFR.Methods We developed a new exogenous biomarker, visible fluorescent injectate (VFI), consisting of a large 150-kD rhodamine derivative and small 5-kD fluorescein carboxymethylated dextrans. After a single intravenous injection of VFI, plasma volume and mGFR can be determined on the basis of the plasma pharmacokinetics of the rhodamine derivative and fluorescein carboxymethylated dextrans, respectively. In this study involving 32 adults with normal kidney function (n=16), CKD stage 3 (n=8), or CKD stage 4 (n=8), we compared VFI-based mGFR values with values obtained by measuring iohexol plasma disappearance. VFI-based mGFR required three 0.5-ml blood draws over 3 hours; iohexol-based mGFR required five samples taken over 6 hours. Eight healthy participants received repeat VFI injections at 24 hours.Results VFI-based mGFR values showed close linear correlation with the iohexol-based mGFR values in all participants. Injections were well tolerated, including when given on consecutive days. No serious adverse events were reported. VFI-based mGFR was highly reproducible.Conclusions The VFI-based approach allows for the rapid determination of mGFR at the bedside while maintaining patient safety and measurement accuracy and reproducibility.

Intraoperative Detection of Leakage Using Topical Fluorescein Following Free Flap Inset in Head and Neck Reconstruction.

In microsurgical head and neck reconstruction, a watertight closure following flap inset is essential to prevent saliva leakage and subsequent complications, such as wound dehiscence and fistulas. However, no standard method has been established to detect and localize the leakage following flap inset. The authors introduce a simple, easy, mobile, and inexpensive method to intraoperatively detect the leakage using topical fluorescein sodium mixed saline and Wood lamp. This simple procedure will allow surgeons to be confident of watertight closure.

A new fluorescence imaging technique for visualizing hepatobiliary structures using sodium fluorescein: result of a preclinical study in a rat model.

BACKGROUND: Near-infrared fluorescence imaging has been recently applied in the field of hepatobiliary surgery. Our objective was to apply blue light fluorescence imaging to cholangiography and liver mapping during laparoscopic surgery. Therefore, we designed a preclinical study to evaluate the feasibility of using blue light fluorescence for cholangiography and liver mapping in a rat model. METHODS: Sodium fluorescein solution (1 mL to each individual) were administered intravenously to 20 male Sprague-Dawley rats (6 weeks old, 200-250 g), after laparotomy. Whole abdominal organs were observed under blue light (at a wavelength of 440-490 nm) emitted from a commercialized LED curing light. RESULTS: Immediately after the tracer solution was administered into the circulatory system of the rat, it was possible to visualize the location of the kidneys and the bile duct under blue light emitted from the light source. The liver was vaguely stained green by the tracer, while the ureters were not. After establishing biliary retention via duct clamping in the left lateral segment of the liver, the green color of the segment became distinct by the tracer, which showed vague coloration following release of the clamp. CONCLUSION: We established the preclinical basis for using blue light fluorescence cholangiography and liver mapping in this study. The clinical feasibility of these techniques during laparoscopic cholecystectomy and hepatectomy remained to be demonstrated.

Photography-based method for assessing fluorescein clearance test in dogs.

BACKGROUND: The fluorescein clearance test (FCT) provides insight into the tear film dynamics. The purpose of this study was to describe an inexpensive and practical method for assessing FCT in dogs, using photography and software analysis, and to assess the retention time of 1 vs. 2 eye drops on the canine ocular surface. METHODS: (i) In vivo - Eight healthy German Shepherd dogs were recruited. Following topical anesthesia with 0.5% proxymetacaine, each eye sequentially received (1 week apart) either 1 drop (35 µL) or 2 drops (70 µL) of 0.5% fluorescein. A Schirmer strip was inserted in the ventral conjunctival fornix for 10 s at the following times: each 10 min for 100 min, 24 h, 48 h and 72 h. (ii) In vitro - Schirmer strips were placed for 10 s in contact with microplate wells containing 1 or 2 drops of 0.5% fluorescein. In both experiments, the fluorescein-impregnated Schirmer strips were immediately imaged, and the area and intensity of fluorescein uptake were analyzed with ImageJ software. For the in vitro experiment, images were evaluated by the same examiner (repeatability) or two examiners (reproducibility). RESULTS: Photography-based FCT was easy to perform and showed high repeatability and reproducibility (coefficients of variation ≤2.75%). In vivo, the area and intensity of fluorescein uptake on Schirmer strips were significantly greater at 30 min and 40 min post- fluorescein instillation in the 2 drops vs. 1 drop groups (p ≤ 0.044). Compared to baseline, the residual fluorescein uptake on Schirmer strips was < 5% at 60 min and 90 min in the 1 drop and 2 drops groups, respectively. CONCLUSIONS: Photography-based FCT is a practical and reliable diagnostic tool with various clinical and research applications in veterinary medicine. Instillation of two drops provided greater amount and longer retention on the anesthetized canine ocular surface than a single drop. Fluorescein clearance time of a single drop in dolichocephalic dogs is 60 min.