Teaching Old Dyes New Tricks: Biological Probes Built from Fluoresceins and Rhodamines.

Small-molecule fluorophores, such as fluorescein and rhodamine derivatives, are critical tools in modern biochemical and biological research. The field of chemical dyes is old; colored molecules were first discovered in the 1800s, and the fluorescein and rhodamine scaffolds have been known for over a century. Nevertheless, there has been a renaissance in using these dyes to create tools for biochemistry and biology. The application of modern chemistry, biochemistry, molecular genetics, and optical physics to these old structures enables and drives the development of novel, sophisticated fluorescent dyes. This critical review focuses on an important example of chemical biology-the melding of old and new chemical knowledge-leading to useful molecules for advanced biochemical and biological experiments.

Assessing the degree of hepatic ischemia-reperfusion injury using physiologically based pharmacokinetic modeling of sodium fluorescein disposition in ex vivo machine-perfused livers.

Ischemia-reperfusion injury (IRI) is an intrinsic risk associated with liver transplantation. Ex vivo hepatic machine perfusion (MP) is an emerging organ preservation technique that can mitigate IRI, especially in livers subjected to prolonged warm ischemia time (WIT). However, a method to quantify the biological response to WIT during MP has not been established. Previous studies used physiologically based pharmacokinetic (PBPK) modeling to demonstrate that a decrease in hepatic transport and biliary excretion of the tracer molecule sodium fluorescein (SF) could correlate with increasing WIT in situ. Furthermore, these studies proposed intracellular sequestration of the hepatocyte canalicular membrane transporter multidrug resistance-associated protein 2 (MRP2) leading to decreased MRP2 activity (maximal transport velocity; Vmax) as the potential mechanism for decreased biliary SF excretion. We adapted an extant PBPK model to account for ex vivo hepatic MP and fit a six-parameter version of this model to control time-course measurements of SF in MP perfusate and bile. We then identified parameters whose values were likely insensitive to changes in WIT and fixed them to generate a reduced model with only three unknown parameters. Finally, we fit the reduced model to each individual biological replicate SF time course with differing WIT, found the mean estimated value for each parameter, and compared them using a one-way ANOVA. We demonstrated that there was a significant decrease in the estimated value of Vmax for MRP2 at the 30-min WIT. These studies provide the foundation for future studies investigating real-time assessment of liver viability during ex vivo MP.NEW & NOTEWORTHY We developed a computational model of sodium fluorescein (SF) biliary excretion in ex vivo machine perfusion and used this model to assess changes in model parameters associated with the activity of MRP2, a hepatocyte membrane transporter, in response to increasing warm ischemia time. We found a significant decrease in the parameter value describing MRP2 activity, consistent with a role of decreased MRP2 function in ischemia-reperfusion injury leading to decreased secretion of SF into bile.

A systematic review and meta-analysis of diagnostic performance of fluorescein-guided sentinel lymph node biopsy in early breast cancer.

BACKGROUND: Evaluation of axillary lymph nodes status in cN0 axilla is performed by sentinel lymph node biopsy (SLNB) utilizing a combination of radioactive isotope and blue dye or alternative to isotope like Indocyanine green (ICG). Both are very resource-intensive; which has prompted development of low-cost technique of Fluorescein Sodium (FS)-guided SLNB. This systematic review and meta-analysis evaluate the diagnostic performance of FS-guided SLNB in early breast cancer. OBJECTIVES: The objective was to evaluate the diagnostic performance of FS for sentinel lymph node biopsy. METHODS: Eligibility criteria: Studies where SLNB was performed using FS. INFORMATION SOURCES: PubMed, EMBASE, Cochrane library and online clinical trial registers. Risk of bias: Articles were assessed for risk of bias using the QUADAS-2 tool. SYNTHESIS OF RESULTS: The main summary measures were pooled Sentinel Lymph Node Identification Rate (SLN-IR) and pooled False Negative Rate (FNR) using random-effects model. RESULTS: A total of 45 articles were retrieved by the initial systematic search. 7 out of the 45 studies comprising a total of 332 patients were included in the meta-analysis. The pooled SLN-IR was 93.2% (95% confidence interval [CI], 0.87-0.97; 87% to 97%). Five validation studies were included for pooling the false negative rate and included a total of 211 patients. The pooled FNR was 5.6% (95% confidence interval [CI], 2.9-9.07). CONCLUSION: Fluorescein-guided SLNB is a viable option for detection of lymph node metastases in clinically node negative patients with early breast cancer. It achieves a high pooled Sentinel Lymph Node Identification Rate (SLN-IR) of 93% with a false negative rate of 5.6% for the detection of axillary lymph node metastasis.

Validation of retinal oximetry vessel selection using fluorescein angiography in patients with optic disc drusen.

Retinal oximetry could provide insights into the pathophysiology of optic nerve disease, including optic disc drusen (ODD). Vessel selection for oximetry analysis is based on morphological characteristics of arterioles and venules and supported by an overlay of estimated blood oxygen saturations. The purpose of this cross-sectional study was to determine the validity of this vessel selection procedure by comparing it with vessel selection supported by video fluorescein angiography (FA). The study included 36 eyes of 36 patients with ODD who underwent retinal oximetry (Oxymap retinal oximeter T1) followed by FA (Heidelberg Spectralis). Two trained graders selected vessel segments in a pre-defined measurement area around the optic disc. One of these graders additionally performed the vessel segment selection with the support of FA images. When performed by the same grader, FA-supported and non-FA-supported vessel selection did not lead to significant differences in total vessel segment length, estimated oxygen saturations or vessel diameters (all p > 0.05). Inter-grader differences were found for arterial and venous segment lengths and arterial saturation (p < 0.05). A similar tendency was found for the arteriovenous saturation difference (p = 0.10). In conclusion, identifying vessel segments for retinal oximetry analysis based on vessel morphology and supported by a color-coded saturation overlay appears to be a valid method without the need for invasive angiography. A numerically small inter-grader variation may influence oximetry results. Further studies of retinal oximetry in ODD are warranted.

Antimicrobial, antioxidant, cell imaging and sensing applications of fluorescein derivatives: A review.

Fluorescein itself is a synthetic organic compound and a prominent member of the xanthene dye family. It exhibits strong fluorescence under ultraviolet (UV) or blue light excitation, making it widely used in various applications, including fluorescence microscopy, flow cytometry, immunoassays, and molecular biology techniques. One of the reasons fluorescein derivatives are highly valuable is their tunable fluorescence properties. Through chemical modifications of the fluorescein structure, different functional groups or substituents can be introduce, altering the compound's fluorescence characteristics such as emission wavelength, intensity, and photo stability. This flexibility allows for tailoring of fluorescent probes to specific experimental requirements, enhancing their utility in a range of scientific disciplines. Fluorescein derivatives also possess excellent antimicrobial and antioxidant activity. This review sheds light on the significant impact of fluorescein derivatives as biological active compounds, highlighting their potential in designing new therapeutic agents with antimicrobial properties. Additionally, their role as antioxidants is discussed. A major aspect covered in the review is the application of fluorescein derivatives as powerful cell imaging probes. Their unique fluorescent properties make them valuable tools for visualizing cellular structures and processes, opening up new possibilities for studying cellular dynamics and interactions.

Comparative efficacy and safety of sodium fluorescein-guided surgery versus standard white light for resection of brain metastases: a systematic review and meta-analysis.

PURPOSE: Recent studies have investigated if the sodium fluorescein-guided (SFg) improves the extent of resection of BMs when compared to standard white light (sWL). Therefore, we aimed to assess the comparative efficacy and safety of SFg and sWL for resection of BMs. METHODS: We searched Medline, Embase, and Cochrane Library databases following Cochrane and PRISMA guidelines for studies reporting comparative data of SFg and WL resection of BMs. We pooled odds ratios (OR) with 95% confidence intervals under random effects and applied I² statistics and leave-one-out sensitivity analysis to assess heterogeneity. I² > 40% was considered significant for heterogeneity. RESULTS: Five studies involving 816 patients were included, of whom 390 underwent BMs resection with SFg and 426 with sWL, and ages ranging between 26 and 86.2 years old. Analysis revealed a statistically significant higher likelihood of complete resection in the SFg group when compared to the sWL group (OR = 2.15, 95%CI: 1.18-3.92, p = 0.01; I² = 47%). Sensitivity analysis revealed a consistent result in all five scenarios, with low heterogeneity in two of the five scenarios. Three studies reported significant improvement in OS in the SFg group, and the qualitative assessment of complications and procedure-related mortality did not provide sufficient information for conclusions. CONCLUSION: This systematic review and meta-analysis identified a higher likelihood of complete resection in the SFg group when compared to the standard sWL group. This study is the first to directly compare the impact of SFg and sWL on resection outcomes for BMs.

Retinal artery occlusion in young patients without typical cardiovascular risk factors: etiologies, prognosis, and suggested work-up.

PURPOSE: To understand the etiology, work-up, and secondary systemic and ocular events of retinal artery occlusion (RAO) in young patients (≤ 45 years old) without typical cardiovascular risk factors. METHODS: Retrospective longitudinal case series of 18 young patients with RAO and without typical cardiovascular risk factors evaluated at the University of Michigan Medicine Health System between the year 2000 and 2022. Laboratory and imaging studies performed at the time of RAO diagnosis, along with systemic and ocular events during follow-up, were recorded. These data were combined with data from a literature review of 74 similar patients experiencing a RAO. RESULTS: Fifteen (83%) of patients were female and 10 (56%) suffered a branch retinal artery occlusion (BRAO). 56% of patients had one risk factor associated with cryptogenic stroke, most commonly a migraine history (33%). The most frequent etiology of RAO was vasculitis (28%), followed by idiopathic (22%) and patent foramen ovale (PFO, 17%). Three out of four patients with idiopathic RAOs developed new migraines around the time of RAO diagnosis, whereas none of the patients with a clear etiology had new onset migraines (n = 14). No patients suffered a stroke or myocardial infarction (MI) in the follow-up period (average 3.6 years ± 3.2 years). Two patients (11%) suffered a repeat RAO, both of whom were diagnosed with a vasculitis. Patients with isolated retinal vasculitis required repeat fluorescein angiograms for up to 2 years after the initial event to definitively identify the vasculitic etiology of the RAO. When our data are pooled with similarly healthy patients from previously published RAO series, structural/functional cardiac abnormalities and vasculitides are the most common identifiable etiologies for RAOs in this group. CONCLUSION: The most common identifiable etiologies of RAO in young patients with low cardiovascular risk are structural/functional cardiac abnormalities and vasculitides, with a small range of additional causes/associations accounting for remaining cases. We suggest a focused work-up algorithm to rapidly identify etiologies in this group while minimizing unnecessary testing. The long-term risk of systemic or ocular secondary events in these patients is low regardless of the etiology of their RAO.

Demyelinating plaque-associated uveitis.

PURPOSE: To report the clinical and fluorescein angiographic (FA) features of demyelinating plaque-associated uveitis (DPU), a subset of uveitis in which patients have demyelinating plaques on the brain/cervical magnetic resonance image (MRI) but do not meet the criteria for multiple sclerosis (MS). METHODS: In this retrospective observational study, Persian Patients were diagnosed with DPU and included if (1) they never satisfied the MS criteria, (2) all other possible etiologies were excluded, and (3) they were followed for at least 2 years. RESULTS: After a median follow-up of 3 years (interquartile range, 2.0-5.3), 8 out of 40 (20%) patients diagnosed with DPU were excluded as they subsequently met the MS criteria. Of remaining 32 patients studied, the mean age was 36.3±9.9 (range 20-56 years), and 30 (93.8%) were female. Twenty-four (75.0%) showed bilateral involvement and 27 (84.4%) had insidious-chronic course. Uveitis was classified as intermediate (with or without anterior uveitis) in 29 (90.6%) and isolated anterior in 3 (9.4%) patients. Nine (28.1%) patients had at least one systemic neurological complaint. Ocular findings were: granulomatous keratic precipitates in 43/44 (97.7%) eyes; snowballs in 25/52 (48.1%) eyes; snowbanks in 4/52 (7.7%) eyes; cystoid macular edema in 20/56 (35.7%) eyes; and optic neuritis in 5/56 (8.9%) eyes. Visual acuity was ≥ 20/40 in 39 eyes (69.6%) at presentation which improved to 46 eyes (81.2%) at 2-year follow up. The two most frequent findings in FA were optic disc leakage/staining in 44/52 (81.5%) eyes, and peripheral retinal perivascular leakage in 39/52 (76.9%) eyes, which in 14/52 (26.9%) eyes extended beyond the equator. CONCLUSION: DPU usually presents as a bilateral chronic granulomatous intermediate and, less often, isolated anterior uveitis, especially in females. Most are neurologically asymptomatic. Visual outcome is generally favorable. In FA, peripheral retinal perivascular leakage is common. DPU patients have an increased tendency to develop MS and should be prohibited from anti-TNF treatment.

Reassessment of arterial versus venous perfusion of diabetic retinal neovascularization using ultrawide-field fluorescein angiography.

PURPOSE: The purpose of this study was to assess whether diabetic NV is perfused by the arterial or the venous circulation. METHODS: This is a retrospective, consecutive case series evaluating patients with proliferative diabetic retinopathy (PDR) imaged with ultrawide-field (UWF) fluorescein angiography (FA). Areas of neovascularization elsewhere (NVE) and neovascularization of the disc (NVD) were assessed. Perfusion was defined as arterial, arteriovenous, or venous if the area of diabetic neovascularization (NV) began to hyperfluoresce either prior, during, or after laminar venous flow, respectively. RESULTS: A total of 180 eyes from 176 patients with 928 NV were identified (830 NVE, 98 NVD). Of those, 5.1% of NVE were classified as arterial and 58.2% of NVD were classified as arterial. The remaining NV were classified as arteriovenous except for a small subset (6.1%) which were indeterminate. None of the NV were classified as venous. Noteworthy examples demonstrated NV that nearly fully perfused prior to any detectable fluorescence within nearby veins as well as clear shunting of blood from a feeding artery to a draining vein. CONCLUSIONS: UWF FA images suggest that some NV is perfused by retinal arteries. This may be useful in devising strategies for early detection and treatment of NV precursors. KEY MESSAGES: What is known • Diabetic retinal neovascularization has long been thought to be perfused by the retinal venous circulation. • Vascular endothelial growth factor has been shown to play key roles in both angiogenesis and arteriogenesis. What is new • Ultrawide-field fluorescein angiography demonstrates that at least some diabetic neovascularization is perfused by the retinal arterial circulation. • This supports the hypothesis that diabetic neovascularization may arise from arterially-perfused intraretinal microvascular abnormalities in the capillary bed.

Relationship between ischemic index, leakage index, and macular edema in branch retinal vein occlusion.

PURPOSE: To investigate the combined association of the ischemic index and leakage index with macular edema on ultra-widefield fluorescein angiography (UWFFA) in patients with branch retinal vein occlusion (BRVO). METHODS: Retrospective image analysis study. The leakage index and ischemic index were calculated using Fiji after aligning early and late UWFFA images. Differences in the ischemic index, leakage index, and central macular thickness (CMT) between ischemic and non-ischemic BRVO were compared. Moreover, the association between the ischemic index, leakage index, and macular edema was analyzed. RESULTS: Eighty-three patients with BRVO were enrolled, including 53 non-ischemic BRVO and 30 ischemic BRVO patients. No significant differences were observed in leakage index and CMT between ischemic BRVO and non-ischemic BRVO (all P > 0.05). In all included patients, CMT correlated with the panretina and all subregion leakage indexes (all P < 0.01), but not with the ischemic index (all P > 0.05). In the ischemic BRVO group, CMT showed a correlation with the leakage index in several regions, but not with the ischemic index. After adjusting for the ischemic index and other clinical features, CMT remained significantly correlated with the leakage index in all regions. CONCLUSION: The leakage index may be a more effective biomarker for monitoring BRVO-associated macular edema compared to the ischemic index. Further follow-up studies are warranted to validate these findings.

Impact of preocular and ocular circulatory dynamics on the vascular density of retinal capillary plexuses and choriocapillaris.

PURPOSE: To highlight the influence of preocular and ocular vascular circulatory dynamics on the vascular density (VD) of retinal capillary plexuses (RCPs) and choriocapillaris (CC) in patients with and without cardiovascular risk (CVR) factors. METHODS: A retrospective observational study in patients with and without CVR factors (type 1 and 2 diabetes, arterial hypertension, and hypercholesterolemia). Fluorescein (FA) and indocyanine (ICGA) angiography circulatory times were arterial time (FAAT), start (FAstartLF) and end (FAendLF) of laminar flow, and arterial time (ICGAAT), respectively. OCT angiography VDs were superficial (VDSCP) and deep (VDDCP) RCPs and CC (VDCC) VDs. Correlation and regression analysis were performed after adjusting for confounding factors. RESULTS: 177 eyes of 177 patients (mean age: 65.2 ± 15.9 years, n = 92 with and 85 without CVR) were included. VDSCP and VDDCP were significantly inversely correlated with FAAT, FAstartLF and FAendLF likewise VDCC with ICGAAT. Correlations were stronger in patients without CVR than with CVR. CVR, FAAT, FAstartLF and FAendLF were more strongly correlated with VDDCP than VDSCP. FAAT, FAstartLF and FAendLF significantly impacted VDSCP and VDDCP, likewise ICGAAT impacted VDDCP. VDDCP was most strongly impacted by FAAT and FAstartLF. CONCLUSION: Ocular and pre-ocular circulatory dynamics significantly impacted RCPs and CC VDs, especially deep RCP.

Detection sensitivity of fluorescence lifetime imaging ophthalmoscopy for laser-induced selective damage of retinal pigment epithelium.

PURPOSE: To investigate the sensitivity of fluorescence lifetime imaging ophthalmoscopy (FLIO) to detect retinal laser spots by comparative analysis with other imaging modalities. METHODS: A diode laser with a wavelength of 514 nm was applied with pulse durations of 5.2, 12, 20, and 50 µs. The laser pulse energy was increased so that the visibility of the laser spot by slit-lamp fundus examination (SL) under the irradiator's observation covers from the subvisible to visible range immediately after irradiation. The irradiated areas were then examined by fundus color photography (FC), optical coherence tomography (OCT), fundus autofluorescence (AF), FLIO, and fluorescein angiography (FA). The visibility of a total of over 2200 laser spots was evaluated by two independent researchers, and effective dose (ED) 50 laser pulse energy values were calculated for each imaging modality and compared. RESULTS: Among examined modalities, FA showed the lowest mean of ED50 energy value and SL the highest, that is, they had the highest and lowest sensitivity to detect retinal pigment epithalium (RPE)-selective laser spots, respectively. FLIO also detected spots significantly more sensitively than SL at most laser pulse durations and was not significantly inferior to FA. AF was also often more sensitive than SL, but the difference was slightly less significant than FLIO. CONCLUSION: Considering its high sensitivity in detecting laser spots and previously reported potential of indicating local wound healing and metabolic changes around laser spots, FLIO may be useful as a non-invasive monitoring tool during and after minimally invasive retinal laser treatment.

Cryopreservation-enhanced differentiation capacity of embryogenic cultures of Castanea mollissima.

A cryopreservation protocol has been developed for embryogenic cultures (ECs) of Castanea mollissima, an important economic species of the Castanea genus in China. We achieved 100 % regrowth when ECs were treated with Plant Vitrification Solution 2 (PVS2) for 30, 60 and 90 min on ice. Optimal PVS2 treatment for cryopreservation was determined to be 30 min on ice based on the highest biomass regrowth after thawing. Fluorescein diacetate (FDA) staining could rapidly and reliably determine post-thaw cell viability and its use facilitated the optimization of the cryopreservation protocols. Although the proliferation rate of the re-established ECs remained largely unchanged compared to non-cryopreserved ECs, the capacity of the re-established ECs to differentiate (on two media) into somatic embryos nearly doubled to approximately 2200-2300 globular somatic embryos per 1 g of re-established ECs. Based on cell cluster size analysis, this enhanced growth is primarily attributed to the presence of significantly greater cell clusters with a diameter of 100-200 µm, which have the highest level of differentiation ability. In order to understand the increased embryogenic potential following cryopreservation, we analyzed the expression of key genes related to somatic embryogenesis. Genes CmWUS and CmABP1 were downregulated while CmLEC1, CmAGL15, CmGRF2, and CmFUS3 were upregulated in re-established ECs when compared to non-cryopreserved ECs.

Frosted branch angiitis in a patient with systemic juvenile idiopathic arthritis: a case report.

BACKGROUND: Frosted branch angiitis is a retinal vascular condition that is associated with a viral infection or autoimmune disorders like Crohn's disease, systemic lupus erythematosus, and Behcet's disease. Frosted branch angiitis presents with vascular inflammation, retinal edema, and severe retinal vascular sheathing. We present a case of systemic juvenile idiopathic arthritis, an autoinflammatory disease, presenting with frosted branch angiitis. REPORT OF CASE: A 14-year-old female with systemic juvenile idiopathic arthritis and a history of bilateral anterior uveitis developed acute unilateral vision loss and was found to have frosted branch angiitis complicated by branch retinal vein occlusion. She underwent an extensive serology workup and aqueous viral PCR to rule out other possible autoimmune and viral etiologies for forested branch angiitis. She received systemic and intravitreal antiviral treatment due to positive CMV IgM initially. However, the clinical picture improved following the use of a higher dose of oral steroids and the switch of the immunosuppressive agent to a TNF-a inhibitor. CONCLUSION: To our knowledge, this would be the first case in the literature demonstrating a systemic juvenile idiopathic arthritis patient presenting with frosted branch angiitis. Infectious causes still must be ruled out, especially CMV, as it is the most common cause of secondary frosted branch angiitis.

Fluorophores in Endoscopic Neurosurgery.

The complexity of intracranial anatomy and pathologies warrants the optimization of multimodal techniques to ensure safe and effective surgical treatment. Endoscopy is being more widely implemented in intracranial procedures as an important visualization tool, as it can offer panoramic views of deep structures while reducing the invasiveness of approaches. Fluorophores are frequently utilized to augment the identification of intracranial anatomic landmarks and pathologies. This chapter discusses the integration of these two surgical adjuncts, highlighting the key fluorophores used in endoscopic neurosurgery and their clinical applications.

A light in the darkness: sodium fluorescein-assisted peripheral nerve sheath tumors resection - a comprehensive systematic review and single-arm meta-analysis.

The treatment for peripheral nerve sheath tumors (PNSTs) is based on surgical excision and the primary goal is to improve symptoms whilst preserving neurological function. In order to improve this technique, surgeons may use sodium fluorescein (SF) to help visualize the neoplasm and, consequently, facilitate its removal. Aiming to assess the efficacy of this emerging surgical strategy, we conducted a systematic review and single-arm meta-analysis. We conducted a systematic search on the PubMed, Embase, and Web of Science databases, following the PRISMA guidelines. Studies without outcomes of interest, case series with less than four patients, letters, comments, technical notes, editorials, reviews, and basic research papers were excluded. The outcomes considered for this study were: the number of tumors that achieved total resection, subtotal resection, or near total resection, the approach/technique utilized by the surgeon, SF-related complications, and total complications. Five studies, with a total of 175 individuals, were included in our survey. Notably, 70% of the neoplasms presented by the patients were schwannomas. Considering extracranial lesions, we found a proportion of 96% (95% CI: 88 - 100%) in total resection, 0% (95% CI: 0-1%) in near total resection, and 4% (95% CI: 0-12%) in subtotal resection, all linked to an amount of 185 analyzed PNSTs. Furthermore, a proportion of 1% (95% CI: 0 - 2%) in SF-related complications was spotted among 183 patients. Finally, total complications analysis accounted for 11% (95% CI: 0 - 25%) among 183 individuals. We concluded that SF-assisted resection of PNSTs is a suitable and relatively safe technique, linked to minimum complications, of which the majority was not associated with the chemical compound itself. Future research is necessary to increase the number of patients available in the current literature and, therefore, enhance future analyses.

Multimodal Imaging in Retinal Vasculitis.

BACKGROUND: Retinal vasculitis is an inflammatory condition that affects the retinal blood vessels. SUMMARY: It can manifest as an idiopathic disorder or be secondary to various infectious or non-infectious diseases, mimicking syndromes, isolated ocular disorders, or drug-induced reactions. Recognizing its distinctive features is crucial for early diagnosis and accurate treatment. This review aimed to demonstrate the variety of tools available to detect disease activity, assess complications, measure the extent of retinal damage, and guide therapy effectively. KEY MESSAGE: This review article highlights the use of multimodal imaging in the comprehensive evaluation of retinal vasculitis.

An Update on Noninfectious Retinal Vasculitis.

BACKGROUND: Retinal vasculitis (RV) signifies the inflammation of various retinal vessels. Noninfectious RV differs from infectious RV with regard to its pathogenesis and treatment. It can have varied clinical presentations and may be associated with systemic vasculitic diseases. SUMMARY: Noninfectious RV can be caused due to type-III hypersensitivity reactions, increased expression of intracellular adhesion molecules, and genetic susceptibility. Noninfectious RV is primarily classified on the basis of the type of retinal vessels involved. It can be further classified as an occlusive or nonocclusive. RV can be a major association of systemic diseases like Behcet's disease, sarcoidosis and systemic lupus erythematosus. Newer modalities, like ultra-widefield fundus fluorescein angiography, can help in the management of RV. Effective treatment of noninfectious RV requires anti-inflammatory and immunosuppressive therapy. The patients may require treatment with high-dose corticosteroids and biological agents. Anti-vascular endothelial growth factor injections and laser photocoagulation may be indicated to treat the occlusive disease. Prompt treatment may prevent complications like vitreous hemorrhage, neovascular glaucoma, and tractional retinal detachment. The treatment more often requires a multidisciplinary approach. KEY MESSAGES: This review provides a comprehensive update on the various causes of noninfectious RV, including both systemic and isolated ocular conditions. It also details various complications and management strategies for this condition.

Sodium fluorescein-guided resection of brain metastases: A needed approach or an option? A systematic review and meta-analysis.

PURPOSE: Brain metastases (BM) often leave residual tumors despite having visible margins, which increases the risk of local tumor recurrence and can impact overall patient survival rates. Fluorescence-guided surgery (FGS) utilizing sodium fluorescein (FL) has been reported as an effective technique in recent studies. This study aimed to evaluate the efficacy of FL FGS in improving the extent of resection of brain metastases and its impact on overall survival. METHODS: We conducted a systematic search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Our primary focus was on gross total resection (GTR). Additionally, we extracted survival data and evaluated the risk of bias using a modified version of the Joanna Briggs Institute critical appraisal tool. RESULTS: The study comprised 970 patients with brain metastases through eight different studies. The study found that patients who underwent FL-guided resection had a significantly higher rate of GTR (OR: 2.02, 95% CI: 1.14-3.56, p = 0.0156, I2 = 41.5%). Additionally, the study concluded that FL-guided resection is associated with better overall survival rates (HR: 0.61, 95%CI: 0.47 0.80, p = 0.0003, I2 = 41.5%). CONCLUSION: Our research suggests that the use of FL is associated with a higher rate of GTR and improved overall patient survival. None of the studies we reviewed reported significant complications associated with the use of FL in patients.

Visualization of the Plasmid DNA Delivery System by Complementary Fluorescence Labeling of Arginine-Rich Peptides.

Cell-penetrating peptides, such as arginine-rich peptides, encapsulate nucleic acid drugs and deliver them to intracellular compartments. Comprehensive tracking of drug delivery systems (DDSs) provides information about the behavior of the drug as well as the fate of the drug carrier after drug release, which is crucial for minimizing side effects. In this study, we labeled peptides designed to carry plasmid DNA with two types of dyes, traditional dye fluorescein and aggregation-induced emission (AIE) dye tetraphenylethylene, and subsequently tracked the DDS through the complementary ON and OFF fluorescence behaviors of the dyes. Traditional fluorescent dyes are susceptible to aggregation-caused quenching during bioimaging, a problem that is mitigated by using AIE dyes. However, by using both of these contrasting fluorescent labels, we were able to clearly visualize the DDS at different stages of its deployment, from drug transport and delivery to carrier dissociation and migration, demonstrating the feasibility of accurate DDS visualization by complementary fluorescence labeling.