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The main causes for cerebrospinal fluid (CSF) leaks are known to be traumatic, iatrogenic, neoplastic, a meningoencephalocele, congenital bone defects, and spontaneous. Off-label intrathecal administration of fluorescein is widely used to localize a CSF leak. Complications are rare and low dose administration is described to be safe. In this case report, we present a case of a patient, who showed a CSF leak due to an encephalocele. Low dose fluorescein was applied intrathecally via lumbar catheter, the CSF leaks could be identified, and multilayered closure was performed. Postoperatively, the patient presented with motor and sensory deficits in the lower limbs which regressed only partially within 2 months. A possible explanation may be an increased local concentration of fluorescein, possibly on the basis of a preexisting lumbar spinal canal stenosis. To our knowledge, this is the first case in which a dose as low as 20 mg of fluorescein (2% saline mixture) led to persisting paraplegia. Therefore, the potential benefits and risks of the intrathecal fluorescein use in the detection of a CSF leak have to be discussed comprehensively prior to surgery.

Background: Contrast-induced nephropathy (CIN) is a common cause of acute kidney injury (AKI), and can be diagnosed when the etiology of AKI is unclear other than via a contrast agent. Fluorescent angiography (FAG) with fluorescein sodium dye is generally considered to be safe for patients with kidney diseases. However, it remains unresolved whether or not FAG can induce CIN., Methods: Patients from two tertiary hospitals who underwent FAG and had serum creatinine results within 4 weeks before FAG and 3 days after FAG between 2001 and 2017 were retrieved. Cases with concurrent iodinated contrast imaging or undergoing dialysis were excluded from the analysis. CIN was defined by two criteria: CIN criteria as >0.5 mg/dL or >25% increase in serum creatinine (sCr) level within 3 days after FAG, and contrast-induced acute kidney injury (CIAKI) criteria as ≥0.3 mg/dL increase within 2 days or ≥50% increase within 7 days after FAG., Results: A total of 979 patients were screened, and we found 124 patients with AKI after FAG. After excluding 32 patients with clear causes of AKI other than FAG, the incidence rates of CIN were 7.3% by CIN criteria and 6.4% by CIAKI criteria. CIN incidence had a U-shaped distribution according to chronic kidney disease (CKD) stages in CIN criteria, while linear association between CIN incidence and CKD stages were found in CIAKI criteria. Kaplan-Meier curves showed the CIN group was significantly associated with end-stage renal disease (ESRD) progression (log-rank P < 0.001, in both CIN criteria and CIAKI criteria), and adjusted hazard ratios by multivariable Cox regression were 2.23 [95% confidence interval (CI) 1.468-3.378] in CIN criteria and 2.17 (95% CI 1.462-3.232) in CIAKI criteria., Conclusions: According to CIN and CIAKI criteria, FAG may cause CIN and appeared to be a possible risk factor for ESRD progression. However, CIN or CIAKI criteria themselves may overestimate AKI and require meticulous attention to the interpretation of results., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Objectives: Intra-operative fluorescein video angiography (FL-VA) has been given increasing attention recently and several studies reported its high utility in neurovascular surgery. The aim of this study was to evaluate the safety of FL-VA in a prospective, single-center cohort of patients operated due to cerebral aneurysms., Patients and Methods: This is an observational cohort study including 150 patients operated due to intracranial aneurysms. The study group consisted of 70 consecutive patients operated with the use of fluorescein video angiography. Post-operative acute kidney injury (AKI) occurrence as well as systemic adverse reactions were reported and further compared with 80 matched controls where FL-VA was not used. Statistical analysis was performed using non-parametric tests (Fisher's exact test)., Results: Post-operative AKI was observed in 17,1% of patients in the study group with only half presenting with acute functional impairment. All of these patients presented initially due to aneurysm rupture. Pre-existing renal dysfunction and hypertension occurred in 16,7% and 33,3%, respectively. No systemic complications following FL-VA were reported. When compared to matched controls, no statistically significant difference regarding AKI occurrence was observed between these two patient populations., Conclusion: Intra-operative fluorescein video angiography proved to have a good safety profile in our cohort. The results of this study suggest that post-operative acute kidney injury observed in patients with subarachnoid hemorrhage is not related to fluorescein use., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: To compare the degree of tear film instability and severity of meibomian gland dysfunction between subjects who use eyeliner and those who do not use eyeliner., Methods: This cross-sectional study included 42 healthy volunteer women who had no dry eye symptoms (Ocular Surface Disease Index score < 13) and aged between 18 and 40 years. The subjects were classified into 2 groups: an eyeliner-use group (EL: regularly used eyeliner ≥3 d/wk and continuously used ≥6 mo) and a noneyeliner-use group as controls. A questionnaire for ocular surface symptoms using a visual analog scale was administered. Then, a number of eye tests were performed [grading of conjunctival inflammation, fluorescein tear breakup time, ocular surface fluorescein staining, Schirmer I, evaluation of meibomian gland (MG) function, detection of eyelid margin abnormalities, and Demodex detection]., Results: Tear breakup time was significantly lower in the EL group compared with controls (3.0 ± 1.9 vs. 5.8 ± 2.1 s, P < 0.001). MG grading was significantly higher in the EL group than in controls (P = 0.004); higher grade (grades 2-3) was found in 85.7% of EL and 47.6% of controls. Meiboscore was also higher in EL than in controls (P = 0.001). Regarding the morphological changes in lid margin, only telangiectasia was detected significantly more in EL (28.6%) compared with controls (4.8%) (P = 0.041). Conjunctival inflammation was observed 4 times more in EL (66.7%) than in controls (14.3%), P = 0.001. Other outcomes included ocular surface symptoms and fluorescein staining scores, and Schirmer I and Demodex detection were not significantly different between both groups., Conclusions: The regular use of eyeliner induces tear film instability and MG dysfunction.

Objective: Sodium fluorescein (FL) is widely used as a fluorescent tracer for brain tumor resection. However, FL-guided resection of spinal gliomas has been reported only occasionally. To evaluate the safety, characteristics, and usefulness of FL-guided surgery in the resection of spinal glioma., Methods: Between January 2015 and December 2018, 220 consecutive patients with 227 spinal gliomas underwent FL-guided resection using the Zeiss Pentero 900 surgical microscope with an integrated YELLOW 560 filter. FL evaluation and clinical outcomes were analyzed., Results: No FL-related complications occurred in this series. Entire tumor fluorescence was observed in 161 (70.93%) gliomas, nodular fluorescence in 46 (20.26%) tumors, and no fluorescence in 20 (8.81%) tumors. The intraoperative fluorescence of 217 (95.59%) gliomas was highly correlated with preoperative contrast-enhancing magnetic resonance imaging, except in eight ependymomas, one pilocytic astrocytoma, and one diffuse midline glioma. Gross-total resection was achieved in 78.85% (179/227) of spinal gliomas, including 94.30% (149/158) ependymal tumors and 43.48% (30/69) astrocytic and oligodendroglial tumors. At the final clinical follow-up, the spinal function of 75 (33.04%) patients showed significant improvement, 105 (46.26%) showed stabilization, and 47 (20.70%) showed deterioration., Conclusion: FL is a safe and useful real-time tool that could enhance tumor borders or residual tumors and hence increase the gross-total resection rate in cases with contrast-enhanced tumors., Competing Interests: Disclosure The authors report no conflict of interest concerning the material or methods used in this study or the findings specified in this paper., (© 2020 Elsevier Inc. All rights reserved.)

Background: Fluorescein angiography is an important and frequently used diagnostic tool in ophthalmological practice. In this case report we describe a patient who experienced an anaphylactic reaction after the injection of fluorescein. Furthermore, we report an interference with laboratory testing by fluorescein in this patient and summarize the literature on this topic., Case Presentation: An 86-year old Caucasian woman undergoing fluorescein angiography due to suspected peripapillary neovascularizations collapsed after the injection of fluorescein. The patient developed an anaphylactic reaction. With fluid resuscitation and oxygen therapy, the patient regained consciousness after a few minutes. The patient was admitted to the geriatric ward for observation, and routine blood and urine tests were performed. Urine protein concentration appeared to be falsely increased as a consequence of disturbance of the laboratory analysis by the presence of fluorescein., Conclusions: Serious complications can occur with fluorescein angiography, such as an anaphylactic reaction. In the case of anaphylaxis appropriate supportive measures including the use of oxygen and epinephrine (e.g. EpiPen), should be available to prevent morbidity and mortality from this test. Furthermore, these potential complications should be taken into consideration when choosing the healthcare setting for fluorescein angiography, such as the immediate availability of an acute medical team. Several studies have demonstrated the interference of laboratory analyses by fluorescein. The majority of these studies were published 10 to 30 years ago. By presenting this case, the authors hope to bring renewed attention to this phenomenon among clinicians, as falsely increased or decreased laboratory values can result in unnecessary diagnostics and/or therapy.

Background: Schwannomas are the most frequent peripheral nerve sheath tumors and are treated by surgical resection when symptomatic. Tumor removal is performed by intraneural dissection and enucleation. In order to safely remove the tumor from the nerve, the use of sodium fluorescein has recently been proposed to distinguish the tumor from the adjacent normal nerve fibers, before incision of the tumor pseudocapsule and during intraneural tumor dissection., Methods: We report a consecutive case series of 5 peripheral nerve schwannomas operated in 4 patients, in which we evaluate the usefulness of sodium fluorescein compared to usual visual landmarks, at each step of the surgical procedure., Results: After exposition of the schwannoma, sodium fluorescein helped with the localization of intracapsular en passant nerve fascicles in only one case. Hence, the definition of a safe entry zone for capsular incision relied mainly on nerve monitoring and direct visualization of en passant nerve fascicles under microscope. During intraneural dissection, there was a sharp contrast between the fluorescent tumor and the non-fluorescent adjacent pseudocapsule in most cases but the colorimetric variation between tumor and normal tissue induced by fluorescence did not outperform the natural contrast between the yellow true capsule and the gray-red layers of the pseudocapsule., Conclusion: Based on these results, we consider that the limited additional value of sodium fluorescein in primary peripheral nerve schwannoma surgery does not warrant its use in daily clinical practice. Additional studies are needed to assess its usefulness during the surgery of recurrences and tumors which are intertwined with several fascicles of origin such as neurofibromas.

We reviewed literature on adverse reactions to intravenous fluorescein angiography using PubMed and found 78 articles in English from 1961 to 2017. The reported rates of adverse reactions were overall 0.083-21.69%, separated into mild (1.24-17.65%), moderate (0.2-6%), and severe (0.04-0.59%). There were 1:100,000 to 1:220,000 deaths. Fluorescein concentration, volume injected, speed of injection, temperature, and contaminants were not correlated with the incidence of reactions. Patient characteristics including other comorbid diseases, allergy history, age, race, and gender showed only an increased rate of reaction in patients with a history of reaction to fluorescein. Although a number of studies examine techniques to reduce adverse reactions to intravenous fluorescein angiography, to date, the only proven method is reviewing allergy history, specifically a history of previous reaction to fluorescein., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose : The aim of this study was to perform a histopathological assessment of the efficacy of sclerosing agents in dacryocystosclerotherapy (DCST) and to evaluate its role as an alternative to dacryocystectomy (DCT) in a specific group of patients. Methods : Thirteen lacrimal drainage systems of 10 patients with primary acquired nasolacrimal duct obstruction (PANDO) were studied. All patients were awaiting a DCT, indications being repeated attacks of dacryocystitis with severe systemic or ocular co-morbidities and/or refusal for a dacryocystorhinostomy. Fluorescent labelled sodium tetradecyl sulphate (SDS) or bleomycin were used as sclerosing agents for a DCST taking specific precautions. All patients underwent a DCT after 4 weeks and histopathological evaluation was performed to assess the changes and extent of DCST. Results : There were nine females and one male, and all patients were above the age of 60 years. Of the 13 lacrimal systems studied, the mean duration of PANDO was 1.3 years. All the patients had associated systemic and/or ocular co-morbidities. SDS and bleomycin were used in 6 and 7 lacrimal systems, respectively. The mean doses used for SDS and bleomycin were 0.26 and 0.31 cc, respectively. The post-injection phase was uneventful except for one patient who had a moderate inflammation, which resolved with low dose oral steroids. Histopathological features were more marked in the SDS group and included loss of epithelium, luminal closure, gross fibrosis across the lacrimal sac wall, congestion and hyalinization of blood vessels, and multiple areas of haemorrhages in the sac wall. Conclusions : DCST is a safe and effective alternative to DCT in very carefully selected patients. Histopathology demonstrates SDS to be more effective as compared to bleomycin.

Aim: To investigate the effects of fluorescein-sodium on neural tissues., Material and Methods: Twenty-one Wistar rats were randomly divided into three experimental groups: control (group 1) and fluorescein-sodium groups with different doses (groups 2 and 3). In the control group, craniectomy following with durotomy was performed with the help of a loupe microscope, and a dry sponge was overlayed to the brain tissue. In the study groups, the open dura was covered with a sponge soaked with 0.02 mg (group 2) and with 0.2 mg (group 3) fluorescein sodium following craniectomy. Three weeks postoperatively, rats were sacrificed for the histopathologic evaluations., Results: Fluorescein-induced apoptosis occurs in a dose-dependent manner in rats' neurons. It was determined that neuron and neuroglial cell TUNEL staining was statistically different among the three groups (p < 0.001). Our results indicated that fluorescein induces apoptosis, resulting in increased nuclear factor kappa beta (NF-kβ) expression in a dose-dependent manner., Conclusion: Fluorescein sodium is used frequently during surgery for CSF fistulas. However, information in the literature about its safety is insufficient. Our study holds promise for the development of new studies on the reliability of this agent.

Objectives: The extent of resection is an independent predictor of prognosis in patients with glioblastomas. Although fluorescein sodium may enhance intraoperative visualization of tumor margin and increase the extent of glioblastoma, the dose related anaphylactic reaction is still a major concern. In the present study, we used allergy skin testing to exclude the patients susceptible to anaphylaxis preoperatively, and then investigated the feasibility of low-dose fluorescein sodium to guide glioblastoma resection intraoperatively, thereby to improve the safety of fluorescein-guided glioma resection., Patients and Methods: Patients with suspected glioblastoma based on brain MRI were subjected to allergy skin intradermal tests for fluorescein sodium preoperatively. Only those with negative allergy skin tests received intravenous injection of low dose fluorescein sodium (1-2 mg/kg) during microsurgical tumor resection under dedicated Yellow 560 filter. The degree of fluorescent staining was documented and the extent of resection was evaluated by MRI scan., Results: One patient with positive allergy skin test was excluded from fluorescein sodium administration and no anaphylactic reaction was found during fluorescein sodium guided surgery in the patients who were negative for allergy skin tests. The low dose fluorescein sodium (1-2 mg/kg) could provide enough visualization of tumors with sufficient discrimination from surrounding normal brain tissue and improve the resection extent of glioblastoma., Conclusion: Preoperative allergy skin test is a useful method to exclude the patients susceptible to anaphylaxis, together with intraoperative low dose fluorescein sodium administration, may facilitate glioblastoma resection by fluorescence guidance while avoid safety concern of dose-related anaphylaxis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Water soluble "vital" dyes are commonly used clinically to evaluate health of the ocular surface; however, staining mechanisms remain poorly understood. Recent evidence suggests that sublethal damage stimulates vital dye uptake by individual living cells. Since cell damage can also stimulate reparative plasma membrane remodeling, we hypothesized that dye uptake occurs via endocytic vesicles. In support of this idea, we show here that application of oxidative stress to relatively undifferentiated monolayer cultures of human corneal epithelial cells stimulates both dye uptake and endocytosis, and that dye uptake is blocked by co-treatment with three different endocytosis inhibitors. Stress application to stratified and differentiated corneal epithelial cell cultures, which are a better model of the ocular surface, also stimulated dye uptake; however, endocytosis was not stimulated, and two of the endocytosis inhibitors did not block dye uptake. The exception was Dynasore and its more potent analogue Dyngo-4a, both small molecules developed to target dynamin family GTPases, but also having off-target effects on the plasma membrane. Significantly, while Dynasore blocked stress-stimulated dye uptake at the ocular surface of ex vivo mouse eyes when treatment was performed at the same time as eyes were stressed, it had no effect when used after stress was applied and the ocular surface was already damaged. Thus, Dynasore could not be working by inhibiting endocytosis. Employing cytotoxicity and western blotting assays, we went on to demonstrate an alternative mechanism. We show that Dynasore is remarkably protective of cells and their surface glycocalyx, preventing damage due to stress, and thus precluding dye entry. These unexpected and novel findings provide greater insight into the mechanisms of vital dye uptake and point the direction for future study. Significantly, they also suggest that Dynasore and its analogues might be used therapeutically to protect the ocular surface and to treat ocular surface disease., Competing Interests: AW, SJ and MEF are named as inventors on a patent application related to this work, submitted by the University of Southern California entitled “Method to Protect and Seal the Ocular Surface” (United States application 16/103,741, filed Aug 14, 2018). The other authors have no commercial or proprietary interest in any concept or product described in this article.

Background: Recent case reports have indicated that intraocular lenses may be discoloured by systemically or locally applied fluorescein. Since very few data are available on the susceptibility of intraocular lenses to fluorescein, an experimental survey on lens discolouration was performed., Material and Methods: Intraocular lenses fabricated from polmethylmethacrylate (PMMA), silicone, hydrophobic acrylic copolymers, and hydrophilic acrylic copolymers were exposed to 10% fluorescein. Staining effects were determined by standardised quantification of light transmission., Results: Intraocular lenses fabricated from PMMA, silicone, or hydrophobic acrylic copolymer did not exhibit any measurable dye uptake after exposure to fluorescein. Intensive and rapid discolouration occurred in hydrophilic acrylic intraocular lenses. The transmission of blue light was reduced by 22% after 1 second and by 74% after 10 minutes of dye exposure., Conclusions: The results indicate that hydrophilic acrylic intraocular lenses develop rapid and intensive discolouration and reduced light transmission after exposure to fluorescein. Lenses fabricated from other materials (PMMA, silicone, hydrophobic acrylic copolymers) were not discoloured by fluorescein staining., Competing Interests: The authors declare no conflict of interest., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Rates of administration of intravenous sodium fluorescein during cystoscopy have increased since indigotindisulfonate sodium was removed from the market in 2014. Although sodium fluorescein has been extensively evaluated and found to be safe, side effects including anaphylaxis have been observed, with an incidence between 0.05% and 1.0%., Case: We present a case of anaphylactic shock after administration of intravenous sodium fluorescein for the assessment of ureteral efflux in a patient with a history of frequent severe allergic reactions undergoing urethral lysis and cystoscopy for urinary retention. Cardiopulmonary structure and function were evaluated and found to be normal. An elevated serum tryptase level was identified, indicating an anaphylactoid reaction. Timely recognition of symptoms associated with a severe allergic reaction in the setting of hemodynamic instability with prompt supportive and pharmacologic therapy was vital in the patient's recovery., Conclusion: Health care providers must be aware of this potential complication, especially in patients with a history of severe allergic reactions.

Intrathecal injection of fluorescein is a method for repairing cerebrospinal fluid fistulas. The most frequent surgical procedure is endonasal endoscopy and the purpose of injecting this dye is to locate the fistula. The anaesthesiologists usually perform the puncture, therefore it is necessary to review this method and to specify some anaesthetic considerations such as correct dosing, safe management protocols and medical-legal aspects. In this case-report we describe the pre, intra and postoperative protocol of action implemented in our department that basically consists of: obtaining a specific consent, prior neurological/ophthalmologic assessment to rule out hypertension and brain damage, use of corticosteroids and previous antihistamines, choosing the correct dose and concentration of intrathecal sodium fluorescein (maximum 1ml at a concentration of 5% diluted in 9ml of cerebrospinal fluid) and close intra and postoperative monitoring., (Copyright © 2017 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.)

Fluorescein angiography (FA) is an important tool for the diagnosis and management of diabetic retinopathy. However, the safety of fluorescein sodium on renal functions is not fully understood. One hundred type 2 diabetes patients, within the Ophthalmology Outpatient Clinic at Alexandria Main University Hospital, Egypt, were enrolled in this prospective observational study to determine the safety of FA on renal function. Serum creatinine and cystatin C were measured pre- and 2 days post-FA. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) was measured pre- and 4 hours post-FA. Renal injury was defined as a 25% increase in serum creatinine, cystatin C, or uNGAL. The study included 71 females and 29 males, with a mean age of 55.73 ± 7.29 years. Baseline serum cystatin C and uNGAL were 0.89 ± 0.34 mg/L and 21.7 ± 2.39 ng/mL, respectively. Serum cystatin C and uNGAL significantly increased after FA to 0.95 ± 0.36 and 27 ± 2.81, respectively (P <0.001). Eleven patients (11%) experienced more than a 25% rise in serum cystatin C from baseline, whereas 40 patients (40%) experienced more than a 25% increase in uNGAL levels after FA. However, the mean serum creatinine level did not change significantly after FA (P = 0.061). Only one patient experienced more than a 25% rise in serum creatinine from baseline. FA showed a significant increase in early sensitive acute kidney injury biomarkers (as serum cystatin C and uNGAL) in substantial number of patients, suggesting but still not proving, a potential harmful effect of FA on kidney functions. These findings were not demonstrated using ordinary serum creatinine.

Objective: To compare different modalities to aid in the evaluation of intraoperative ureteral patency on cystoscopy in the postindigo carmine era., Methods: In a randomized controlled trial, participants undergoing pelvic surgery were randomized into one of four groups: saline distention (control), 10% dextrose distention, oral phenazopyridine, or intravenous sodium fluorescein. Our primary outcome was visibility of the ureteral jets. Secondary outcomes included surgeon satisfaction; adverse reactions including allergies, urinary tract infections, urinary retention, cystoscopy times, and ureteral obstruction; and delayed diagnosis. Participants were followed for 6 weeks. A sample size of 176 participants was planned to demonstrate a 30% difference in the visibility scale. All analyses were performed in an intention-to-treat fashion., Results: From February 25, 2015, through August 2015, 176 participants were enrolled; 174 completed the trial, and two did not undergo intervention. Forty-four participants were included in the phenazopyridine, dextrose, saline, and sodium fluorescein groups. Sodium fluorescein and 10% dextrose resulted in significantly improved visibility and satisfaction when compared with the control group (P<.001 and P=.004, respectively). Dextrose provided the highest satisfaction and phenazopyridine provided lowest, but visibility was not statistically different between the two groups (P=.101). Three ureteral obstructions were identified intraoperatively and none in the postoperative period. Mean total cystoscopy time varied between 4.0 and 4.8 minutes and postoperative urinary retention rate was 50% across all groups. Overall urinary tract infection rate was 24.1%, which was similar between interventions. There were no related adverse events., Conclusion: Compared with the control, 10% dextrose and sodium fluorescein resulted in improved visibility and provided significantly more satisfaction in the evaluation for ureteral patency with no considerable increase in operative time or morbidity., Clinical Trial Registration: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02476448.

Background and Aims: Image quality can be guaranteed with the conventional dosage of fluorescein sodium in probe-based confocal laser endomicroscopy (pCLE). However, yellow discoloration of the skin seriously affects daily life and simultaneously increases the risk of adverse events such as allergic reactions. The aim of this study was to test whether a lower dosage of fluorescein sodium can provide satisfactory image quality and to compare the diagnostic accuracy of gastric intestinal metaplasia (GIM) through a randomized blind controlled trial., Methods: Consecutive patients were randomly assigned to different doses of fluorescein sodium. Image quality was determined by the endoscopists' subjective assessments and signal-to-noise ratio (SNR) assessment systems. Skin discoloration was tested using a neonatal transcutaneous jaundice detector. In addition, consecutive patients with a known or suspected diagnosis of GIM were examined by pCLE with the lower dose and the traditional dose., Results: Only 0.01 mL/kg dose of 10% fluorescein sodium led to a significant decrease in image quality (P < .05), and a dose of 0.02 mL/kg had the highest SNR value (P < .05). There were no significant differences in skin discoloration between the 0.01 mL/kg and 0.02 mL/kg doses (P = .148) and no statistical difference in the diagnostic accuracy of pCLE for GIM between the 0.02 mL/kg and 0.10 mL/kg doses (P > .05). The kappa values for the correlation between pCLE and histopathology were 0.867 (95% confidence interval, 0.782-0.952) and 0.891 (95% confidence interval, 0.811-0.971)., Conclusions: The 0.02 mL/kg dose of 10% fluorescein sodium seems to be the best dose for pCLE in the upper GI tract, with comparable image quality with the conventional dose and insignificant skin discoloration. This dose is also very efficient for the diagnosis of GIM., (Copyright © 2016 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Objectives: To assess (i) the adverse reactions (ARs) associated with intravenous fluorescein angiography (IVFA); (ii) the relationship between a known history of IVFA-associated AR and ARs on the subsequent IVFA test; and (iii) the dose-response relationship between intravenous sodium fluorescein (NaFl) injection and ARs associated with IVFA., Design: Retrospective chart review., Participants: A total of 2247 patients with 3381 consecutive IVFAs between May 2013 and April 2014., Methods: Fisher's exact tests or χ 2 tests were used to compare the percentage difference of IVFA-associated ARs for different categorical variables. Logistic regressions were used to assess the relationship between a known history of IVFA-associated AR and any AR(s) on a subsequent IVFA test., Results: The overall percentage for IVFA-associated ARs was 3.3%. Adjusted for age and sex, patients who had a previous IVFA-associated AR(s) were 6.2 times more likely (adjusted odds ratio 95% CI 3.4-11.2, p < 0.0001) to have an AR compared to those who did not. Among 17 patients who had 2 repeated IVFA tests and an AR on the first IVFA test, the rate of AR on the second test was lower in patients who received a reduced dosage of NaFl (n = 14) compared to those with the standard dosage (n = 3) (35.7% vs 66.7%); however, this finding was not statistically significant (p = 0.5368)., Conclusions: The rate of IVFA-associated ARs in this study was low. Patients who had a known IVFA-associated AR were more likely to re-experience an AR on a subsequent test compared to those who did not. In addition, a reduced NaFl dose did not significantly reduce the chance of experiencing an AR on a subsequent test, which is likely because of the insufficient power of this comparison., (Copyright © 2016 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Objective: The objective of this study is to assess the feasibility of simultaneous Sodium Fluorescein (SF) and Indocyanine Green (ICG) injection during neurosurgical procedures., Patients and Methods: Three patients harboring a high-grade glioma (HGG) were retrospectively identified in the surgical database of the Neurosurgical Unit 2 at the Foundation IRCCS Istituto Neurologico C. Besta in Milan, by having received intraoperatively both SF for tumor resection and ICG for vasculature angiographic studies in the same surgical procedure. We identified 2 males and 1 female (age range 25-60). Lesions were located in the left temporo-polar area and hippocampus (1 case), right superior frontal gyrus (1 case), left supplementary motor area (1 case). All the three lesions showed Magnetic Resonance Imaging (MRI) characteristics of HGG and, for this reason, in all patients a fluorescein-guided tumor removal was proposed. In the same surgical procedure ICG videoangiography was considered necessary in order to study arterial and venous vasculature, given by the strict relation of the tumor with an unexpected Posterior Communicating Artery (PComA) aneurysm in one case and with cortical drainage veins complexes in the other two cases. In all cases a microscope equipped with both YELLOW560 and IR800 integrated filters (Pentero 900, Carl Zeiss, Oberkorchen, Germany) was used. Fluorescein was i.v. injected at a dose of 5mg/kg immediately after patient intubation. ICG was i.v. injected in bolus on demand of the operating surgeon at a dose of 12.5mg., Results: No side-effects related to simultaneous injection of SF and ICG were identified. In all three cases, the use of SF allowed to better visualize the tumor areas during surgical removal, thus leading to a radical resection until no macroscopic appearance of residual tumor mass and no fluorescence was visible in the surgical cavity. ICG videoangiography confirmed the patency of branches of internal carotid artery after clipping of an unexpected small PComA aneurysm found intraoperatively during tumor removal in one case, while in patient 2 and 3 it allowed to evaluate patency and study flow pattern in cortical drainage veins that were intimately related to the tumors and the way of the surgical approach. Postoperative MRI showed a Gross Total Resection of the tumors in all cases., Conclusions: This study showed for the first time the feasibility of intravenous SF injection and ICG videoangiography in the same surgical procedure. The presence of different fluorescence filters on the same surgical microscope allows the surgeon to recognize and safely resect the tumor and simultaneously evaluate local brain vascularization., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Surgical resection is a key element of the multidisciplinary treatment of cerebral metastases (CMs). Recent studies have highlighted the importance of complete resection of CMs for improving recurrence-free and overall survival rates. This study presents the first data on the use of fluorescein sodium (FL) under the dedicated surgical microscope filter YELLOW 560 nm (Zeiss Meditec, Germany) in patients with CM., Methods: Thirty patients with CMs of different primary cancers were included (15 females, 15 males; mean age 61.1 years); 200 mg of FL was intravenously injected directly before CM resection. A YELLOW 560 nm filter was used for microsurgical tumor resection and resection control. Surgical reports were evaluated regarding the degree of fluorescent staining, postoperative MRIs regarding the extent of resection [gadolinium (Gd)-enhanced T1-weighted sequence] and the postoperative courses regarding any adverse effects., Results: Most patients (90.0%, n = 27) showed bright fluorescent staining, which markedly enhanced tumor visibility. Three patients (10.0%) (two with adenocarcinoma of the lung and one with melanoma of the skin) showed no or only insufficient FL staining. Another three patients (10.0%) showed residual tumor tissue in the postoperative MRI examination. In two other patients, radiographic examination could not exclude the possibility of very small areas of residual tumor tissue. Thus, gross-total resection was achieved in 83.3% (n = 25) of patients. No adverse effects were registered over the postoperative course., Conclusions: FL and the YELLOW 560 nm filter are safe and practical tools for the resection of CM, but further prospective research is needed to confirm that this advanced technique will improve the quality of CM resection.

Fluorescein is a chemical dye frequently used in eye diseases to assess blood flow in the retina, choroid tissue, and iris. Although it has many known adverse effects, it has not previously been reported to lead to jaundice. The purpose of this case report was to emphasize that for patients presenting at the emergency department with jaundice symptoms, it should not be forgotten by emergency physicians that jaundice can develop after fluorescein angiography. Case: A 65-year-old woman presented at the emergency department with extensive jaundice that had developed on her entire body a few hours after fluorescein angiography applied because of vision impairment. The test results for all the diseases considered to cause jaundice were normal,and fluorescein-related jaundice was diagnosed. Conclusion: A detailed anamnesis should be taken when jaundice is seen in patients who have undergone fluorescein angiography, and it should not be forgotten that fluorescein dye is a rare cause of jaundice.

Anaphylaxis is a severe, potentially fatal, systemic allergic reaction that suddenly occurs after contact with an allergy-causing substance. The aims of this study were to evaluate the clinical characteristics and outcomes of patients who were diagnosed with anaphylaxis to fluorescein. The medical records of patients with anaphylaxis to intravenous fluorescein angiography (IVFA) admitted to the emergency department between January 2010 and June 2012 were retrospectively reviewed. Among 12,005 times of IVFA, a total of 10 patients (0.083 %) were included in this study. The mean age was 58.3 years, and 50.0 % were men. The most common presentation was hypotension (systolic blood pressure <90 mmHg) (70 %) followed by nausea and vomiting (60 %). Especially, patients with diabetes were more prone to develop hypotension and most hypotensive events occurred in less than 3 min. All of our patients recovered without sequelae and mortality following prompt and proper intervention. Although the incidence is low, anaphylaxis due to intravenous fluorescein can occur during IVFA. Physicians should be aware of this possible complication, and be prepared to treat it.

Purpose: To evaluate the safety of oral fluorescein angiography (FA) and to compare its efficacy in detection of macular edema (ME) with spectral-domain optical coherence tomography (SD-OCT)., Methods: Results of imaging studies for 1,928 eyes of 1,019 patients who had simultaneously undergone both oral FA and SD-OCT by a confocal laser ophthalmoscope were reviewed. Sensitivity in detecting ME, discrepancy rate, and "kappa" agreement were determined for both the techniques and with eyes stratified by disease diagnosis., Results: No allergic reactions occurred after oral FA. Mild gastric discomfort was noted in <1% of the patients; 1,840 eyes (95.4%) showed concordance between the two techniques, and kappa agreement was 90.3%. For ME, oral FA showed an overall sensitivity of 0.97 and SD-OCT of 0.91. Equivalent sensitivity was found in cases of wet age-related macular degeneration (0.99). Oral FA was more sensitive than SD-OCT in cases of retinovascular diseases. The SD-OCT showed higher sensitivity in cases of macular holes. Detection of ME by SD-OCT was significantly higher in cases of intense leakage on oral FA (P < 0.001)., Conclusion: Oral FA proved to be a safe and an adequate technique to evaluate ME. It is more sensitive than SD-OCT in detection of ME in cases of retinovascular diseases but can fail to detect ME in cases of macular holes. A noninvasive examination with simultaneous oral FA and SD-OCT may be considered to obtain a comprehensive evaluation of the presence of ME from different pathologies.

Background: Intrathecal injection of fluorescein is a useful adjuvant method for localization of fistulas in endoscopic endonasal repair of cerebrospinal fluid (CSF) leakage. Although being neurotoxic in commercial doses, a low dose of diluted fluorescein seems to be safe on the basis the existing data in the literature., Objectives: The purpose of this study was to investigate the role of a low- dose intrathecal fluorescein injection in detection of CSF fistula and potential adverse effects of this technique., Materials and Methods: CSF rhinorrhea was repaired in 20 patients with an endoscopic endonasal technique. Intraoperative intrathecal fluorescein injection was used for localization of the site of the CSF leak. The accuracy rate of leakage site identification and the incidence of complications and recurrences were recorded., Results: Intrathecal administration of fluorescein demonstrated CSF leakage in 18 of the 20 patients (90%). There were no intraoperative complications. Definitive closure of the CSF leakage site was achieved in 16 patients (80%) after the initial reconstruction. Recurrence occurred in four cases and all patients were free of CSF leakage after the second surgical attempt., Conclusions: The present study suggested that a low dose of intraoperative intrathecal fluorescein administration is a safe and sensitive method for localization of CSF leakage sites.

We report a patient with severe anaphylactic shock immediately after injection of i.v. fluorescein. The patient recovered without sequela. Immunoglobulin E (IgE) mechanism was highly suggestive with significant increase in serum tryptase, positive basophil allergen threshold sensitivity (CD-sens) and histamine release tests towards fluorescein. This is, to our knowledge, the first report where CD-sens has been used to aid in diagnosing an IgE-mediated anaphylactic shock caused by fluorescein., (© 2012 The Authors. Acta Anaesthesiologica Scandinavica © 2012 The Acta Anaesthesiologica Scandinavica Foundation.)

Purpose: To examine the safety of outpatient clinic simultaneous intravenous fundus fluorescein angiography (IVFA) and indocyanine green angiography (ICGA) in patients with any/all drug allergy history., Methods: In a single-center retrospective study conducted from February 2007 to March 2011, 390 consecutive outpatients with drug allergy history and 3426 patients without allergy history underwent simultaneous intravenous IVFA and ICGA. The detailed drug allergy history, the symptoms and time of the adverse reaction during simultaneous IVFA and ICGA were recorded in all the patients., Results: Of the 390 patients with drug allergy history who received IVFA and ICGA, 28 patients (7.2%) had an adverse reaction. In contrast, 145 of the 3426 patients (4.2%) without allergy history had an adverse reaction during simultaneous IVFA and ICGA. Statistical significance in the incidence (P=0.008) and severity (P=0.001) of the adverse reaction was observed between patients with drug allergy history and those without drug allergy history. In 390 patients with drug allergy history, no statistical significance was indicated in the incidence of the adverse reaction among different types of drug allergy (P>0.05)., Conclusions: Simultaneous IFVA and ICGA are generally safe procedures with an acceptable incidence of an adverse reaction. However, patients with drug allergy history may have a higher incidence and greater severity of an adverse reaction.

Fluorescein is associated with minor adverse effects during retinal angiography, and most of these effects are not severe and not related to immunological mechanism. However, on rare occasions, anaphylatoid reaction can occur, and fatalities involving fluorescein have been described. Life threatening complications after intravenous injection of sodium fluorescein require immediate intervention. Trainings for professionals are needed to standardize treatment for this event.

This case history deals with an 85-year-old patient who underwent surgery to treat rhinoliquorrhea. The patient aspirated a lutescent fluid shortly after anesthesia was administered. However, this fluid was not gastric juice but cerebrospinal fluid (CSF) running down the nasopharynx. The CSF had been stained with fluorescein prior to surgery in order to help localize the CSF fistula. This case of top down aspiration is discussed and preventive measures which can be employed in order to avoid similar complications in patients with rhinoliquorrhea are presented.

Purpose: To evaluate allergy skin testing as a diagnostic tool of adverse reactions to fluorescein and whether allergy and previous sodium fluorescein angiography (SFA) act as predisposing factors., Methods: Patients with adequate indication for fluorescein angiography and normal skin responsiveness were subjected to allergy skin-prick and intradermal tests for fluorescein, followed by SFA. During SFA, adverse reactions were monitored and classified as mild, moderate or severe. Previous SFAs and adverse reactions as well as the presence of atopy were also registered., Results: One thousand and thirty-seven patients were enrolled in the study and 1284 SFAs were executed. Forty-four patients (4.3%) developed 55 adverse reactions; among them 50 (3.8%) were mild, three (0.2%) moderate and two (0.16%) severe. None of the reactors produced positive skin tests to fluorescein. Patients with atopy and previous SFAs were not more susceptible to adverse reactions., Conclusion: The vast majority of adverse reactions to fluorescein are mild and not attributed to immunological mechanisms. Allergy skin tests cannot predict non-immunological reactions but their utility remains substantial in predicting anaphylaxis during SFAs and must be performed in patients reporting risk factors in their past medical history., (© 2009 The Authors. Journal compilation © 2009 Acta Ophthalmol.)

Purpose: To assess the effect of a combination of proparacaine 0.50%-sodium fluorescein 0.25% and ultrasound (US) pachymetry on central and midperipheral corneal thickness., Setting: School of Optometry and Vision Sciences, Cardiff University, Cardiff, Wales, United Kingdom., Design: Case series., Method: Topographic measurements of corneal thickness in healthy right eyes were obtained using a scanning-slit device (Orbscan IIz) and a Scheimpflug device (Pentacam) before and after application of proparacaine 0.50%-sodium fluorescein 0.25% and US pachymetry. Changes in corneal thickness in the center and 2.5 mm from the center in the temporal, nasal, inferior, and superior locations were assessed., Results: The study evaluated 35 eyes. The scanning-slit and Scheimpflug devices recorded a small but statistically significant increase in corneal thickness at all locations (mean 4.9 ± 14.3 [SD] to 9.1 ± 11.7 μm; P<.05, paired t test). The cornea swelled uniformly across its diameter (scanning slit, P=.934; Scheimpflug, P=.654; analysis of variance); there was no statistically significant difference in the amount of swelling between the 2 devices (P>.05, t test). The 95% limits of agreement were broad (-10 to +30 μm), suggesting a large degree of interindividual variability., Conclusions: Ultrasound pachymetry combined with proparacaine 0.50%-sodium fluorescein 0.25% caused a small (<10 μm) but significant amount of corneal swelling on average. Because the effect on corneal thickness may be greater than -10 to +30 μm in individual cases, clinicians should avoid contact procedures before obtaining topographic maps of corneal thickness using scanning-slit and Scheimpflug devices., (Copyright © 2011 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

We present a male patient who underwent a fluorescein sodium-guided brain tumor excision and experienced an anaphylactic reaction with severe hypotension and bradycardia. A 54-year-old, 70 kg man of American Society of Anesthesiologists status II was seen with a history of glioma. In the 80th minute of the operation, 20 mg/kg intravenous (i.v.) fluorescein sodium was injected after dural opening. A few minutes later, the anaphylactic reaction was diagnosed. Surgery was ended and the patient was delivered to the intensive care unit with intubation. Laboratory values were: immunoglobulin E, 332 U (upper limit 100 U); and elevated tryptase, 3.12 mg/dL. In view of the expanding use of fluorescein sodium in clinical procedures, physicians should be alerted to this rare but life-threatening adverse event., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Indocyanine green (ICG) and fluorescein dyes were inadvertently injected into an antecubital artery during angiography. Apart from a slightly longer arm to retina time, ICG angiography was uneventful. In contrast, intra-arterial injection of fluorescein resulted in a dramatic yellowish discoloration of the arm distal to the injection site that was combined with stinging pain. Fluorescence of both dyes in the forearm could be recorded using a confocal scanning laser ophthalmoscope. The angiographic retinal image quality appeared normal. After about 5 hours, the skin discoloration had disappeared and there were no late complications.

A 34-year-old Lebanese man presented with photophobia, tearing, and reduced vision in the left eye, a few hours after being accidentally hit in the eye with a fingernail. The cornea in the left eye showed corneal defect . About three minutes after receiving topical fluorescein in this eye, the patient developed syncope and anaphylactic shock. After immediate reanimation, the patient regained consciousness. When specifically asked, he reported a three-month history of urticaria to the right side of his neck and nose. The possible pathophysiology involves an underlying IgE-mediated mechanism. Ophthalmologists should be aware of complications associated with topical fluorescein.

Background: There are only few reports about confocal laser endomicroscopy (CLE) for pulmonary imaging. In these studies, in contrast to gastrointestinal endoscopy, CLE was performed without fluorescein., Objectives: The aim of the present study was to evaluate the value of fluorescein usage for CLE of the lung., Methods: Fluorescein-aided CLE was performed in 15 consecutively recruited patients and in 4 young healthy volunteers with a miniprobe during flexible bronchoscopy. Before and after intravenous administration of fluorescein, central airways and alveolar structures were evaluated., Results: Fluorescein administration did not permit imaging of epithelial cells in the central airways. In the lung periphery, alveolar walls and partially macrophages could be seen in native imaging, as expected. After administration of fluorescein, alveoli were almost filled with foam in areas with normal lung tissue. The origin of this foam was shown to be artificial. Furthermore, in patients with pathologies of the lung parenchyma, dark neoplastic and inflammatory cells adjacent to the alveolar walls were identified. No relevant side effects of fluorescein administration could be observed., Conclusions: Fluorescein-aided CLE of the lung appeared to be safe and well tolerated. While the lack of staining of cells in the central airways was a major limitation, it permitted analysis of the lung interstitium and alveolar space and thus emerges as a new approach for the in vivo analysis of interstitial lung diseases., (Copyright © 2010 S. Karger AG, Basel.)

Background: Confocal laser endomicroscopy (CLE) is rapidly emerging as a valuable tool for gastrointestinal endoscopic imaging. Fluorescent contrast agents are used to optimize imaging with CLE, and intravenous fluorescein is the most widely used contrast agent. Fluorescein is FDA-cleared for diagnostic angiography of the retina. For these indications, the safety profile of fluorescein has been well-documented; however, to date, fluorescein is not cleared for use with CLE., Aims: To estimate the rate of serious and total adverse events attributable to intravenous fluorescein when used for gastrointestinal CLE., Methods: We performed a cross sectional survey of 16 International Academic Medical Centres with active research protocols in CLE that involved intravenous fluorescein. Centres using i.v. fluorescein for CLE who were actively monitored for adverse events were included., Results: Sixteen centres performed 2272 gastrointestinal CLE procedures. The most common dose of contrast agent was 2.5-5 mL of 10% sodium fluorescein. No serious adverse events were reported. Mild adverse events occurred in 1.4% of individuals, including nausea/vomiting, transient hypotension without shock, injection site erythema, diffuse rash and mild epigastric pain. The limitation is that only immediate post procedure events were actively monitored., Conclusions: Use of intravenous fluorescein for gastrointestinal CLE appears to be safe with few acute complications.

Objective: To assess the incidence of anaphylaxis following intravenous fluorescein angiography (IVFA) at 1 satellite clinic., Study Design: Observational case series., Participants: Records from 1400 patients were reviewed., Methods: Consecutive vitreoretinal patients who underwent IVFA between 1998 and 2005 at 1 satellite office were included for retrospective analysis., Results: Anaphylaxis developed in 4 of 1400 (0.3%) patients within minutes after they had received intravenous fluorescein. In each case, the reaction was recognized promptly and treated with injectable epinephrine by the physician, and symptoms resolved quickly. The ambulance was called in all 4 cases. In the literature, reports of 21 cases of anaphylaxis and 7 deaths have been published in the past 55 years., Conclusions: Although uncommon, anaphylaxis as a reaction to intravenous fluorescein does occur. As this is potentially life-threatening, prompt diagnosis and treatment are crucial. An emergency care plan should be available.

Objective: To determine the incidence rate and correlation factors of the adverse reactions during fluorescence fundus angiography (FFA) in special patients., Methods: 256 special patients were performed FFA with Heidelberg Retinal Angiography. Fluorescein Sodium was given according to the body weight and adverse reactions during FFA were observed. The special patients enrolled in this study include those with drug allergy history, system disease, light adverse reactions such as nausea, vomiting and pruritus during the fist FFA or patients over 80 years old., Results: Adverse reactions were observed in 69 of 256 (27.0%) cases and the majority is at a mild to moderate degree. Nausea, sneezing, vomiting or pruritus occurred in 10 of 73 (13.7%) patients with drug allergy history. Nausea or vomiting occurred in 4 of 78 (5.1%) patients with systemic diseases. Different degrees of adverse reactions occurred in 54 of 56 (94.6%) cases who had nausea, vomiting or pruritus during the first FFA. Nausea occurred in 1 of 49 (2.0%) patients over 80 years old., Conclusion: FFA is a safe examination for the above special patients. The incidence rate of adverse reaction due to FFA in these special patients is similar to that in the healthy population. Observing the patients closely and strengthening the containment and salvage measures are important to improve the safety of FFA in these special patients.

Background: Although intravenous fluorescein angiography (IVFA) is a relatively safe procedure, side effects have been shown to occur. The designed purpose of this study was to demonstrate a reduction in the frequency and severity of side effects during digital IVFA using 2 mL compared with 5 mL of 10% sodium fluorescein (NaFl). The secondary hypothesis was to show that no loss of image quality occurred with a reduction in the NaFl dose utilizing digital fluorescein angiography., Methods: A prospective study was initiated in which 1200 patients were randomized to 2 mL or 5 mL of 10% NaFl to allow for the evaluation of adverse events. Standard IVFA technique utilizing modern high-resolution digital photography was employed. Photographers evaluated the difficulty of image capture. A masked observer recorded all adverse events. Masked ophthalmologists evaluated image quality subjectively with a 4-point rating scale. Secondary to concerns regarding image quality, a masked interim analysis was carried out after 140 patients had been randomized., Results: A statistically significant reduction in the quality of angiograms (p = 0.0025) and ease of photography (p = 0.0012) was associated with 2 mL of NaFl, necessitating the termination of the study. Patients randomized to the 5 mL NaFl group experienced all 3 of the minor adverse events in the study. No statistically relevant conclusions could be obtained from this limited group., Interpretation: Two millilitres of NaFl for IVFA produces inferior quality digital images compared with 5 mL of NaFl. The potential reduction in adverse events associated with 2 mL of NaFl becomes unimportant in light of this significant finding regarding image quality.

Cerebrospinal fluid leak (CSF), clinical sign of a dural lesion of the skull base, is a relatively rare event that can present with a variety of symptoms. Every craniosinus fistula should be considered a serious, potentially life-threatening situation (even those cases with hidden CSF leak). Reports of experience concerning diagnosis and treatment of craniosinus fistulae have appeared in the Literature. In the last few years, the endoscopic nasal approach is proving effective as it makes diagnosis much easier and is the least invasive surgical approach, with the greatest percentage of success. Various classifications are being proposed to improve clinical evaluation of CSF leaks and to simplify the diagnostic and therapeutic approach. The most common parameters of classification are: aetiology (traumatic, iatrogenic, non-traumatic, etc.) site, type of flow (high or low pressure) and, as far as concerns treatment, the type of graft used, all of which have contributed to various diagnostic and therapeutic algorithms being proposed. Therefore, the subject seems to be widely schematized and the therapeutic attitude widely agreed. However, one of the diagnostic and therapeutic approaches is now being questioned. For some, it is the heart of the clinical approach, while for others, it is a useful tool yet too dangerous to be used on account of potential side effects: namely, the fluorescein test. This procedure, consisting of intrathecal injection of a colorant (fluorescein), is well known by the Food and Drug Administration (FDA) which neither explicitly prohibits it, nor allows it, intrathecal administration is, therefore, an off label use. As far as the Authors know, authorization of this procedure has not been forthcoming anywhere in the world although the procedure itself is widely employed. As far as concerns the use of intrathecal fluorescein, many scientific papers have been written, clearly supporting its clinical usefulness. One limit to the use of fluorescein derives from frequent reports of complications, often related to the intrathecal administration; such complications are, however, always due to an incorrect dosage. In order to perform correct monitoring of any complication related to the use of intrathecal fluorescein and to investigate in a strictly scientific fashion, the legal problem related to the off label use (intrathecal administration) of an authorised substance, the Authors coordinated an Italian multicentre study aimed at establishig the tolerability of the lumbar intrathecal administration of fluorescein. Aim of the study was to review the literature focusing on CSF leaks, to set up to date diagnostic and therapeutic indications of fluorescein and to report the preliminary results of the Italian multicentre study.

Fluorescein is a fluorochrome dye occasionally administered by intrathecal injection to identify and localize cerebrospinal fluid leaks. Although generally considered to be a benign intervention, intrathecal administration of fluorescein has resulted in adverse events. We report a case of status epilepticus after intrathecal administration of fluorescein. Anesthesia providers should be aware of complications associated with intrathecal fluorescein use and be prepared to manage neurologic complications during the perioperative period.

Purpose: To evaluate the efficacy and safety of orally administered sodium fluorescein to stain the clear vitreous before vitrectomy for proliferative diabetic retinopathy (PDR)., Methods: Twenty-two consecutive eyes of 20 patients with PDR and five eyes of five patients with proliferative vitreoretinopathy (PVR) were included. The average patient age was 52 years (range 46-58). Closed pars plana vitrectomy, proliferative membrane peeling and endolaser photocoagulation were performed. Vitreous and blood samples were collected to measure sodium fluorescein concentrations by high pressure liquefied chromatography., Results: The degree of staining of the clear vitreous was evaluated by colour photographs, videos and the concentration of sodium fluorescein in the vitreous and blood samples. The clear vitreous in all 22 eyes with PDR ranged from slightly to markedly green, but the clear vitreous in five eyes with PVR was not stained with sodium fluorescein. The sodium fluorescein concentration in the vitreous samples ranged from 122 to 282.0 ng/mL and from 64 to 74 ng/mL in the blood samples in patients with diabetes and PVR. No urticaria, nausea or other side-effects developed., Conclusion: The clear vitreous can be stained markedly green by sodium fluorescein administered 12-16 h before surgery. Surgeons can easily differentiate residual clear vitreous. The stained vitreous may be made more visible by photocoagulation. This method is also helpful in teaching surgical procedures, and fewer side-effects compared with intravenous and intravitreal fluorescein and intravitreal triamcinolone.