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  • Fluorescein Staining
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Articles published on Lissamine Green

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  • Research Article
  • 10.1159/000550166
Corneal Fluorescein Staining in FDA-Reviewed Dry Eye Registrational Clinical Trials: Evidence of Limited Endpoint Responsiveness
  • Jan 6, 2026
  • Ophthalmic Research
  • Zeenal Dabre + 8 more

Introduction: Corneal fluorescein (FL) staining is the most widely used efficacy endpoint in dry eye disease (DED) registrational trials, yet dye diffusion and variable readout timing can blur punctate staining, reducing the precision and consistency of grading. We assessed the performance of FL staining as an efficacy endpoint by analyzing endpoint success across FDA-reviewed DED trials and evaluated whether a standardized, diffusion-resistant dye could provide an alternative quantitative measure of corneal staining. Methods: We conducted a synthesis of FDA-reviewed DED registrational clinical trials through April 2025 to determine the proportion of trials that met the corneal FL staining efficacy endpoint. Clinical relevance was assessed using a minimal clinically important difference (MCID) of ≥3 units on the 0–15 National Eye Institute (NEI) scale. In a clinical cohort of 50 DED patients (97 eyes), total corneal staining was compared after sequential instillation of 5 µL of 2% FL (readout ∼2.5 min) and 1% lissamine green (LG) (readout ≤30 s). Results: Among 20 FDA-reviewed registrational trials that prespecified corneal FL staining as an efficacy endpoint, 10 (50%) failed to meet this endpoint. Of the seven trials in which FL staining served as a primary or co-primary endpoint, only one achieved MCID for corneal staining. Across all trials meeting the endpoint, treatment-vehicle differences were small (mean additional reduction 0.4–1.2 units; Cohen’s d < 0.5), indicating that FL staining yielded uniformly small effect sizes. In the clinical cohort, 1% LG produced corneal staining that was strongly associated with 2% FL for mild (ρ = 0.99), moderate (ρ = 0.93), and severe (ρ = 0.69) disease (p < 0.001). Bland-Altman analysis showed that while the mean bias was negligible, the width of the 95% limits of agreement (−1.26 to 0.85) suggests the two corneal staining dyes are not fully interchangeable at the individual-measurement level. Conclusions: Corneal FL staining demonstrates limited responsiveness as an efficacy endpoint in DED registrational trials. Because 1% LG provides corneal staining strongly associated with 2% FL while preserving discrete punctate detail and allowing standardized, early readouts, it may represent a suitable alternative vital dye for future DED efficacy and safety assessments.

  • Research Article
  • 10.36871/vet.zoo.bio.202602105
Техника проведения лиссаминового теста у птиц
  • Jan 1, 2026
  • Veterinariya, Zootekhniya i Biotekhnologiya
  • Lyubov A Solomakhina

Lissamine Green is an organic acid-based ophthalmic dye (E142) with a green color. It is used as a colorant for pharmaceuticals, food products, and cosmetics. It is available as sterile individual test strips for diagnosing epithelial lesions of the cornea and conjunctiva. Lissamine Green ophthalmic diagnostic strips stain only damaged epithelial cells and do not stain the intercellular space. Lissamine Green test strips are indispensable for diagnosing abnormalities in the structure of the precorneal tear film, particularly its mucin and lipid components, which lead to high-quality keratoconjunctivitis sicca, as well as for diagnosing punctate keratitis, herpetic keratitis, and early keratomycosis, which may not stain with fluorescein. Negative dye uptake results from the action of normal tear film components, such as mucin and albumin, which protect epithelial cells from the dye; positive dye uptake represents a tear film abnormality. After comparing two methods we developed for applying lissamine green dye to the ocular surface of birds, we concluded that the first method (applying a dry strip to the conjunctiva) is inconvenient for the clinician, while the second method (instillation of a lissamine solution prepared from a dry strip onto the ocular surface) is ideal for conducting such studies. To prepare the lissamine solution, remove a sterile lissamine green test strip from its individual packaging, tear off the dye-soaked end of the strip, and place it into a 2 ml syringe after removing the plunger. The plunger is then inserted, and 0,5–1,0 ml of sterile 0,9 % sodium chloride solution or water for injection is drawn into the syringe through the needle. Applying a freshly prepared liquid lissamine solution is easy to use, economical, and suitable for birds of all species and eyeball sizes.

  • Research Article
  • Cite Count Icon 1
  • 10.3390/ijms262110782
Allogeneic Umbilical Cord Blood Serum Eyedrops for the Treatment of Severe Dry Eye Disease Patients
  • Nov 6, 2025
  • International Journal of Molecular Sciences
  • Marco Zeppieri + 8 more

Human allogeneic umbilical cord blood serum stands out as a potent adjunct to conventional therapies for ocular surface disorders related to severe Dry Eye Disease. By expediting ocular surface regeneration and fostering epithelial integrity, umbilical cord blood serum not only enhances subjective patient experiences but also improves objective clinical indicators. This makes it particularly useful in patients with corneal ulcers through ocular surface regeneration and anti-inflammatory activity. This retrospective, interventional, non-randomized clinical study aims to explore the efficacy of allogenic umbilical cord blood serum in patients who had previously received other treatments unsuccessfully. This study was a retrospective, non-comparative, interventional clinical study involving 55 patients (35 females and 20 males) aged 18–82 years with severe Dry Eye Disease who were unresponsive to standard treatments. The study was conducted at Eye Center “G.B. Morgagni-DSV”, Catania, Italy. Patients were categorized based on the etiology of severe Dry Eye Disease into four groups: group I consisted of 26 patients with filamentary keratitis and corneal ulcers associated with rheumatologic diseases such as Sjogren’s syndrome and systemic sclerosis; group II comprised 15 patients with graft-versus-host disease; group III consisted of 10 patients with corneal neurotrophic ulcers; group IV included four patients with Steven–Johnson syndrome. Outcomes evaluated before and after treatment were OSDI (Ocular Surface Disease Index) and SANDE (Symptom Assessment in Dry Eye) Questionnaires, VAS (Visual Analog Scale), Slit-Lamp Examination, Esthesiometry, Lissamine Green Staining, NIBUT (Non-Invasive Break-Up Time) and BUT, Fluorescein Staining with Photography and Oxford Classification, Schirmer Test, Best-Corrected Visual Acuity (BCVA), Meibography. We observed a significant improvement in SANDE, VAS and OSDI questionnaires, Schirmer Test, BUT, BCVA, and Oxford classification after treatment with allogeneic cord blood serum eyedrops. Clinical variables, such as corneal inflammation, conjunctivalization, corneal neovascularization, or pain, were also considered individually. Nevertheless, pain and inflammation reduced markedly over time until completely healed in all cases. Our study highlights the remarkable efficacy of allogeneic cord blood serum eyedrops in patients with severe Dry Eye Disease who have shown absent or inadequate response to usual treatments for dry eye. This underscores the need for further comprehensive investigations in this field.

  • Research Article
  • Cite Count Icon 3
  • 10.1007/s40123-025-01168-1
Lissamine Green in Ophthalmology: A Comprehensive Review of Diagnostic and Clinical Applications.
  • Jun 5, 2025
  • Ophthalmology and therapy
  • Stefano Barabino + 12 more

Lissamine green (LG), a diagnostic dye that stains devitalized or damaged epithelial cells, is widely used to assess ocular surface integrity, enabling the detection of inflammation, epithelial defects, and conjunctival irregularities. To explore the diagnostic and clinical applications of LG in ophthalmology, focusing on its use for ocular surface diseases, a group of experts in ophthalmology and optometry participated in an advisory board to share their clinical practice experience with the use of LG. Building on the advisory board contents, this narrative review was based on a combination of expert opinions from the roundtable discussion and a comprehensive review of the current literature. This review highlights the clinical relevance of LG as a diagnostic tool in ocular surface disease and underscores the potential of newer formulations to enhance diagnostic accuracy. In particular, the review highlights the historical development of LG use in ophthalmology and its advantages over other dyes, especially in terms of patient comfort and safety, as well as specific clinical protocols for using LG in assessing dry eye disease severity and inflammatory responses. Additionally, the review examines recent advancements in LG formulations, which enhance their utility in clinical practice, and addresses safety considerations. Potential areas for future research are also discussed, particularly in developing standardized evaluation procedures using artificial intelligence.

  • Research Article
  • Cite Count Icon 4
  • 10.3390/jcm14062022
A Comparison of Physical Characteristics in Different Brands and Staining Techniques in a Brand of Lissamine Green Strips.
  • Mar 17, 2025
  • Journal of clinical medicine
  • Neema Ghorbani-Mojarrad + 19 more

Backgrounds/Objectives: The aim of this study was to compare differences in the physical characteristics of lissamine green (LG) strips and the outcomes of using different staining techniques. Methods: Two separate complementary investigations were conducted. Physical study: Differences between four LG strips were evaluated in terms of material, dye concentration, and dye absorption. In vivo study: Bulbar conjunctival staining was compared for four application methods of I-DEW LG strips presented in a randomized order for twenty-two participants: (1) single application 5 s after wetting (also repeated using GreenGlo for comparison), (2) single application using two strips held together, 5 s after wetting, (3) two applications using a single LG strip 5 s after wetting, 1 minute apart, (4) the same as method 3, with a single fluorescein strip in between LG applications. White light imaging was performed immediately following application and after 30, 60, 90, and 300 s. Three masked practitioners independently evaluated the randomized staining images for spot count and staining intensity. Results: Physical study: Strip paper fibres demonstrated visible similarities, with no difference in saline absorption (p > 0.05). LG concentration increased as saline retention duration increased (F = 964.1, p < 0.001), and GreenGlo tips were significantly darker (F = 2775.2, p < 0.001). In vivo study: I-DEW application resulted in less conjunctival staining than GreenGlo (p < 0.001). Amongst I-DEW application techniques, staining levels were similar (p > 0.05); however, staining intensity was significantly higher following two applications of I-DEW, 1 min apart, compared to a single application (p = 0.042). Both spot count and staining intensity decreased with time (p < 0.001). Conclusions: Two applications of I-DEW using a single strip, 1 min apart, after wetting with a single drop of saline provided maximal staining. There was also a significant difference in staining intensity observed between LG products.

  • Research Article
  • Cite Count Icon 3
  • 10.2147/opth.s498893
Utilizing Corneal Fluorescein and Conjunctival Lissamine Green Staining Combined with in vivo Confocal Microscopy for Grading the Severity of Dry Eye Disease.
  • Mar 1, 2025
  • Clinical ophthalmology (Auckland, N.Z.)
  • Mian Guo + 3 more

To explore the application of corneal fluorescein sodium (CFS)-conjunctival lissamine green (CLG) staining combined with in vivo confocal microscopy (IVCM) in clinical grading of the severity of dry eye disease (DED). Eleven normal persons (4 males and 7 females) and thirty-two mild, moderate, and severe DED patients (aged 22 to 56 years, and mean age 45.4 ± 12.9 years;14 males and 18 females) were included for CFS-CLG staining. The stained positive areas were observed and recorded for the number and morphology of staining points. Subsequently, the morphology and cell density of corneal and conjunctival cells were observed and analyzed by IVCM. CFS-CLG staining revealed that the number of CFS-stained points were not significantly increased in mild DED, and there was a small amount of CLG staining in the temporal bulbar conjunctiva; the CFS-stained points of moderate DED were increased compared with mild DED, and the nasal conjunctiva diffuse small flake CLG staining was observed; the cornea of severe DED had the most fluorescein-stained points, and the conjunctiva diffuse large CLG staining. IVCM examination showed that corneal epithelial basal cell density was significantly decreased, while activated corneal Langerhans cells were significantly increased in moderate and severe DED. Meanwhile, the morphology of superficial stromal cells of cornea became irregular and the cell density decreased significantly in moderate and severe DED. The density of conjunctival goblet cells was also significantly reduced in moderate and severe DED. Moreover, the density of activated conjunctival Langerhans cells increased significantly in mild, moderate, and severe DED. Observing and detecting the morphology and density of corneal epithelial basal cells, superficial stromal cells, corneal Langerhans cells, conjunctival goblet cells, and conjunctival Langerhans cells in positive CFS-CLG stained areas by IVCM, which may be a reliable basis for clinical grading of DED severity.

  • Research Article
  • 10.18231/j.ijceo.2025.026
Study of changes in corneal endothelial cell characteristics in dry eye disease
  • Feb 15, 2025
  • Indian Journal of Clinical and Experimental Ophthalmology
  • Gayatri R Gondhali + 2 more

Corneal endothelial cells, vital for maintaining transparency and unable to regenerate, compensate for cell loss by enlarging adjacent cells, which leads to increased size and varying morphology with age. This study emphasizes how dry eye affects these cells, stressing the need to address this frequently neglected condition. This cross-sectional study explored alterations in corneal endothelial cell characteristics among 33 individuals with dry eye disease (DED) compared to 33 age- and gender-matched controls, aged between 18 and 78 years. Participants underwent comprehensive ophthalmic evaluations, and various grades of DED were diagnosed using the Ocular Surface Disease Index questionnaire, Tear Meniscus Height measurement, Tear Film Break-Up Time test, Schirmer’s I test, and Lissamine Green staining and endothelium cells were assessed for endothelial cell density (ECD), cell morphology and central corneal thickness (CCT) by specular microscopy. Compared to the control group (57.73±8), the average cell morphology showed significant changes in individuals with moderate DED (52±9) with p=0.0497, and in those with severe DED (49±7) with p=0.004. Additionally, Central Corneal Thickness (CCT) was notably lower in the severe DED group (485±32 µm) with p=0.002 as compared to control group (533±34 µm). The mean ECD was lower in severe DED patients compared to controls, but not statistically significantly. The research found a correlation between DED severity and corneal endothelial cell characteristics. Severe DED leads to significant morphological alterations and reduced CCT. These findings highlight DED's impact on corneal cells, emphasizing early detection and intervention for preserving corneal health and improving intraocular surgery outcomes.

  • Research Article
  • Cite Count Icon 2
  • 10.1089/jop.2024.0169
Safety and Efficacy of 0.1% Cyclosporine Solutions in Dry Eye Syndrome: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.
  • Feb 10, 2025
  • Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics
  • Yuri Aleksander-Ivanov + 7 more

Purpose: Cyclosporine A (CsA) is a primary treatment for dry eye disease (DED). Ophthalmic solutions containing CsA are available in concentrations of 0.05%, 0.09%, and 0.1%. While 0.1% CsA solutions have been used to treat DED, their safety and effectiveness remains somewhat uncertain. Therefore, we conducted a meta-analysis to evaluate their safety and efficacy. Methods: We searched PubMed, Cochrane Database, Embase, and Web of Science for randomized controlled trials (RCTs) that compared 0.1% CsA solutions with their vehicle. Statistical analysis was performed using Review Manager 5.4.1. Results: We included six RCTs (2,170 patients) with follow-up periods ranging from 4 weeks to 6 months. A total of 1,119 patients (51.56%) with DED were treated with 0.1% CsA. The mean age of patients was 57.9 ± 4.8 years, with 79.7% being female. The total corneal fluorescein staining (tCFS) at last follow-up [mean differences (MD) -0.49; 95% confidence interval (CI) (-0.73, -0.24); P < 0.0001], at 4 weeks [MD -0.64; 95% CI (-1.07, -0.22); P = 0.003], and central corneal fluorescein staining (cCFS) [MD -0.19; 95% CI (-0.35, -0.03); P = 0.02] scores were lower in patients treated with 0.1% CsA compared with vehicle. The Lissamine Green conjunctival staining (LGCS) [MD -0.51; 95% CI (-0.78, -0.24); P = 0.0002] and ocular surface disease index (OSDI) scores [MD -3.04; 95% CI (-5.84, -0.23); P = 0.03] were lower in the 0.1% CsA group compared with vehicle. Adverse events associated with 0.1% CsA solution in the treatment of DED varied across studies, but were generally mild to moderate. Notably, similar events were also significantly present in the vehicle group, supporting the safety profile of this treatment. Conclusion: Ophthalmic 0.1% CsA seems safe for treating DED, and significantly reduced tCFS, cCFS, LGCS, and OSDI scores compared with vehicle solutions.

  • Research Article
  • Cite Count Icon 1
  • 10.1007/s40123-024-01062-2
Evaluation of the Performance of an Ocular Surface Modulator Containing ST-Lysyal Versus Hyaluronic Acid Eyedrops in Patients with Dry Eye Disease: A Pilot Study
  • Nov 19, 2024
  • Ophthalmology and Therapy
  • Stefano Barabino + 4 more

IntroductionDry eye disease (DED) is a multifactorial condition of the ocular surface, primarily treated with tear substitutes, which do not fully restore natural tear functions. In this pilot study, we tested the hypothesis that T-Lysyal (T-Lys) improves symptoms and signs in patients with DED. Additionally, we provide a literature overview on the effects of T-Lys in ophthalmology and non-ophthalmology conditions to elucidate its mechanisms of action.MethodsA double-masked, randomized pilot study was conducted in patients with DED treated with T-Lys or hyaluronic acid (HA) 0.2% combined with tamarind seeds polysaccharide (control group) for 2 months. Inclusion criteria were a diagnosis of DED with symptoms lasting ≥ 6 months, Symptom Assessment in Dry Eye (SANDE) score ≥ 30, and at least one of the following: fluorescein staining of the cornea (score ≥ 3, NEI scale), conjunctival staining (Lissamine Green, score ≥ 3), or tear breakup time (T-BUT) ≤ 10 s. Data from the right eye were used for statistical analysis. A PubMed literature search of T-Lys studies was also performed without publication year restrictions.ResultsTwelve patients in the T-Lys group and 15 in the control group completed the study (mean age 67 ± 11 years). T-Lys treatment resulted in significant improvements from baseline (V0) to 2 months (V2) in symptoms assessed by visual analogue scale (T-Lys: 4.58 ± 2.57 mm at V0, 2.92 ± 1.38 mm at V2, p < 0.05; control: 5.13 ± 2.29 mm at V0, 5.3 ± 2.4 mm at V2), T-BUT (T-Lys: 2.58 ± 1.31 s at V0, 3.58 ± 1.37 s at V2, p < 0.05; control: 3.07 ± 1.43 s at V0, 3 ± 1.13 s at V2), and corneal staining (T-Lys: 2.16 ± 4.17 at V0, 1.41 ± 3.70 at V2, p < 0.05; control: 1.4 ± 2.19 at V0, 1.4 ± 2.16 at V2). No adverse events were reported. Literature findings supported T-Lys’s efficacy in managing both ophthalmology and non-ophthalmology conditions.ConclusionThis study provides the first clinical evidence of T-Lys efficacy in patients with DED, supporting preclinical data and highlighting its potential as a promising ocular surface modulator.Trial RegistrationThe study was registered in the ISRCTN registry for Clinical Studies with no. 13587929.

  • Research Article
  • Cite Count Icon 3
  • 10.3390/medicina60111764
Umbilical Cord Blood-Derived Products in Autoimmune Systemic Syndromes with Severe Dryness: A Pilot Study
  • Oct 28, 2024
  • Medicina
  • Rosario Foti + 8 more

Background and Objectives: Human umbilical cord blood serum (HUCBS) stands out as a potent adjunct to conventional therapies for ocular surface disorders (OSDs) caused by, among many, autoimmune systemic syndromes. By expediting ocular surface regeneration and fostering epithelial integrity, HUCBS not only enhances subjective patient experiences but also improves objective clinical indicators. This makes it particularly useful in patients with corneal ulcers through ocular surface regeneration and anti-inflammatory activity. This study aims to explore the efficacy of HUCBS in patients who had previously received other treatments unsuccessfully. Materials and Methods: This study was a prospective, non-comparative, interventional case series study involving 49 patients (30 females and 19 males) aged 15–82 years with severe OSDs who were unresponsive to standard treatments. The study was conducted at the San Marco Hospital, Catania, Italy. Patients were categorized into four groups based on the etiology of their severe OSDs: Group I consisted of twenty four patients with filamentary keratitis and corneal ulcers associated with rheumatologic diseases such as Sjogren’s syndrome and systemic sclerosis; Group II comprised thirteen patients with graft-versus-host disease; Group III consisted of nine patients with corneal neurotrophic ulcers; and Group IV included three patients with Steven–Johnson syndrome. The outcomes were evaluated before and after treatment using the following assessments: OSDI (Ocular Surface Disease Index) and SANDE (Symptom Assessment in Dry Eye) questionnaires, VAS (Visual Analog Scale), Slit Lamp Examination, Esthesiometry, Lissamine Green Staining, NIBUT (Non-Invasive Break-Up Time), BUT (Break-Up Time), Fluorescein Staining with Photography and Oxford Classification, The Schirmer Test, Best-Corrected Visual Acuity (BCVA), and Meibography. Results: We observed a significant improvement in the outcomes from the SANDE, VAS, and OSDI questionnaires, The Schirmer Test, BUT, BCVA, and Oxford Classification, after treatment with UCBS. Clinical variables, such as corneal inflammation, conjunctivalization, corneal neovascularization, and pain, were also considered individually. Nevertheless, pain and inflammation reduced markedly over time until complete healing was achieved in all cases. Conclusions: Our pilot study highlights the substantial efficacy of HUCBS in patients with systemic autoimmune diseases who have shown inadequate responses to prior treatments for dry eye. This underscores the need for further comprehensive investigations in this field.

  • Research Article
  • Cite Count Icon 5
  • 10.1016/j.microc.2024.111950
Design of a novel deep eutectic solvent for microextraction of Lissamine green B from food Samples: A green approach
  • Oct 22, 2024
  • Microchemical Journal
  • Nebiye Kizil

Design of a novel deep eutectic solvent for microextraction of Lissamine green B from food Samples: A green approach

  • Research Article
  • Cite Count Icon 8
  • 10.3390/life14101268
Umbilical Cord Blood Platelet Lysate Eyedrops for the Treatment of Severe Ocular Surface Disorders in Graft vs. Host Disease Patients: Clinical Study
  • Oct 5, 2024
  • Life
  • Caterina Gagliano + 9 more

Background: Graft-versus-host disease (GvHD) is an overactive systemic inflammatory response that can arise following allogeneic hematopoietic stem cell transplantation (HSCT). This condition occurs when the transplanted donor immune cells recognize the recipient’s tissues as foreign and trigger an immune response against them. The ocular surface (eyelids, conjunctiva, meibomian glands, lacrimal glands, and cornea) is particularly involved in GvHD, and its response to existing treatments, including potent immunosuppressants and new targeted therapies, is undesirable, with such treatments often being ineffective. Human allogeneic umbilical cord blood platelet lysate stands out as a potent adjunct to conventional therapies for ocular surface disorders related to severe Dry Eye Disease. This study aimed to evaluate the safety and efficacy of umbilical cord blood platelet lysate eyedrops for the treatment of severe ocular surface disorders in graft-versus-host disease patients who have received previous unsuccessful treatments. Methods: This study was a prospective, non-comparative, interventional case series study involving 22 patients (10 females and 12 males) aged 25–46 years with severe ocular surface disorders that were unresponsive to standard treatments. The GvHD patients were categorized based on the severity of their ocular surface disorders into three groups: Group I: five patients with severe Dry Eye Disease and filamentary keratitis; Group II: eight patients suffering from severe blepharo-kerato-epitheliopathy; Group III: nine patients with corneal ulcers. Fresh umbilical cord blood (UCB) was obtained from healthy donors and subjected to centrifugation using a novel PRP preparation kit provided by Sciacca (AG) Cord blood bank, Italy in a one-step process. In all groups, the outcomes before and after treatment were evaluated by means of the OSDI (Ocular Surface Disease Index), SANDE (Symptom Assessment in Dry Eye) questionnaire, VAS (Visual Analogue Scale), slit lamp examination, Esthesiometry, Lissamine Green Staining, the NIBUT (Non-Invasive Break-Up Time) and BUT, fluorescein staining with digital photography and Oxford classification, the Schirmer Test, the Best Corrected Visual Acuity (BCVA), and Meibography. In Group III at each evaluation time, the size of the ulcer and its relative reduction compared to the baseline size were recorded. Clinical variables, such as corneal inflammation, conjunctivalization, corneal neovascularization, or pain, were also considered individually. Results: We observed a significant improvement in the SANDE, VAS, and OSDI scores; Schirmer Test; BUT; BCVA; and Oxford classification after treatment with allogeneic cord blood serum eyedrops. Nevertheless, pain and inflammation reduced markedly over time until complete healing in all cases. The mean reduction in the ulcer surface area (compared to baseline values) was significantly higher at all assessment points (p = 0.001 for day 7 and p < 0.001 for subsequent time points every 30 days for 90 days). At the last check-up (after 90 days of treatment), the number of ulcers (Group III, nine patients) with a reduction in size of greater than 50% was eight (88.8%), of which seven ulcers were completely healed. None of the patients experienced treatment-related local or systemic adverse events. In this study, using a relatively large number of cases, we demonstrated that the use of umbilical cord blood platelet lysate eyedrops is a safe, feasible, and effective curative approach for severe ocular surface disease in patients with GvHD. Conclusions: Our pilot study highlights the remarkable effectiveness of allogeneic cord blood serum eyedrops in patients with severe ocular surface disorders following GvHD who have shown an inadequate response to the usual treatments. It is mandatory to design future studies on the efficacy of this therapeutic approach for acute ocular, mucosal, and cutaneous GvHD.

  • Research Article
  • Cite Count Icon 1
  • 10.2147/opth.s468457
Advantages of Lissamine Green Vital Staining as an Endpoint in Dry Eye Clinical Trials.
  • Aug 1, 2024
  • Clinical ophthalmology (Auckland, N.Z.)
  • John Rodriguez + 6 more

The absence of a standardized diagnostic method for clinical signs of Dry Eye Disease (DED) complicates clinical trials for future treatments. This paper evaluated Lissamine Green (LG) conjunctival staining as a valid, stable and modifiable endpoint for both clinical practice and clinical trials. Screening and pre-randomization data from two identically designed clinical trials for DED resulted in a pooled dataset of 494 subjects. Inclusion was based on reported symptoms, lissamine green (LG) conjunctival staining, Fluorescein (Fl) corneal and conjunctival staining, and Schirmer's Test (ST). Outcome measures were assessed based on the modifiability of LG staining to exposure to a Controlled Adverse Environment (CAE®), correlation of LG to Fl staining, relative variation of LG staining scores and Schirmer test scores, and the correlation of LG staining with symptom scores. The modifiability of LG conjunctival staining to environmental exposure was demonstrated, with nasal LG and FL staining displaying the most similar percent change. Nasal LG conjunctival staining scores for subjects with ST scores of less than 8mm were significantly higher than for subjects with ST greater than 8mm. LG staining scores were more consistent (25% change from baseline threshold) than ST scores. Finally, statistically significant correlations were found between LG staining and a number of symptom scores. This evaluation demonstrates the superiority of the utilization of a clinical endpoint focused on ocular surface damage. The reproducibility and modifiability of LG conjunctival staining to controlled adverse environment, coupled with its significant correlation with symptoms, positions it as an exemplary clinical sign endpoint for clinical management and in clinical trials. Our findings advocate for the adoption of LG conjunctival staining as a primary endpoint in both clinical research and drug development, offering a more effective means of identifying and addressing ocular surface damage in the realm of DED.

  • Research Article
  • 10.2174/1574885518666230822144922
Patented Formulations, Nanotherapeutics and Herbal Compound Applications for Dry Eye : A Review
  • Jun 1, 2024
  • Current Drug Therapy
  • Vindhya Pal + 1 more

Background: The defining features of dry eye syndrome, a frequent tear and ocular surface multifactorial disorder, are changes in the ocular surface epithelia linked with less tear production and elevated sensitivity of the ocular surface, which trigger an inflammatory response. Aqueous deficit dry eye and evaporated dry eye are the two common types of dry eye. A few of the testing methods used to detect Dry Eye Disease are the Schirmer’s test, Tear Meniscus Volume, Tear Break-up Time, Tear Film Thickness, Meibomian Gland Infrared Meibography, Lissamine Green Staining, and Rose Bengal Staining. Hyperosmolarity and instability are the main pathogenic processes of dry eye disease. These systems are intricately linked to one another and create a "vicious circle" that never ends. Objective: The objective of this review was to describe patented formulations, novel drug delivery systems and herbal drugs for Dry Eye Disease. Results: Following a thorough assessment, the current study has elaborated a number of patented formulations in the form of contact lenses, biomarkers, novel approaches, and emulsions (traditional dosage forms) as well as natural medicines. In comparison to standard dosage forms, contact lenses and novel approaches have longer contact times and higher bioavailability. Conclusion: In this paper, the diagnostic methods of dry eye disease, the outcomes of pathophysiology, herbal treatments, nanotherapeutics, and current patented medicine formulations are described.

  • Research Article
  • Cite Count Icon 5
  • 10.1016/j.molliq.2024.124732
Novel Fe-Ti nanoparticles synthesized in deep eutectic solvents for enhanced photo-electro-Fenton processes: Synergistic effects and environmental applications
  • Apr 12, 2024
  • Journal of Molecular Liquids
  • A Puga + 4 more

Novel Fe-Ti nanoparticles synthesized in deep eutectic solvents for enhanced photo-electro-Fenton processes: Synergistic effects and environmental applications

  • Research Article
  • Cite Count Icon 5
  • 10.1080/02713683.2024.2302546
The Long-Term Effect on Dry Eye of Posterior Approach Ptosis Surgery Vs. Upper Eyelid Blepharoplasty
  • Jan 13, 2024
  • Current Eye Research
  • Ofira Zloto + 3 more

Purpose To examine the long-term effect of combined blepharoplasty and Müller muscle-conjunctival resection (MMCR) compared to an upper blepharoplasty procedure on dry eye syndrome. Methods This is a Prospective comparative case series. Two groups of patients participated in this study: the blepharoplasty group included adult patients that underwent blepharoplasty at least 3 years earlier and the ptosis group consisting of adult patients that underwent MMCR with blepharoplasty at least 3 years earlier. The parameters that were compared for all patients before the procedure, on postoperative day 90, and at the long-term follow-up were: Schirmer-test 2, tear break-up time (TBUT), fluorescein staining, and lissamine green (LG) staining. Results The participants included 25 post-MMCR patients with a mean follow-up of 4.94 ± 0.64 years and 15 post-blepharoplasty patients with a mean follow-up of 4.22 ± 0.32 years. There was a significant increase in the postoperative LG and fluorescein staining scores compared to the preoperative scores in the ptosis group (p < .01 and p < .01, respectively) as well as a decrease in postoperative TBUT compared to the preoperative values (p = .044). Those parameters were not significant in the blepharoplasty group. Conclusions Patients who underwent MMCR, but not those following upper blepharoplasty, showed signs of dry eye compared to the preoperative status after long-term follow-up. Dry eye signs should be examined before MMCR surgery, and patients should be aware of the high risk of developing dry eye and the need for long-term treatment. Surgeons should carefully consider performing MMCR for patients with severe dry eye.

  • Research Article
  • Cite Count Icon 3
  • 10.1007/s10895-023-03518-3
Saturable and Reverse Saturable Absorption Features of Lissamine Green Dye in Different Solvent Media.
  • Nov 27, 2023
  • Journal of fluorescence
  • N Srinivasan Arunsankar + 4 more

Organic dyes have shown a remarkable nonlinear optical (NLO) characteristics under low power laser regime because of chemical stability, large nonlinearity and high susceptibility. With this view in mind, herein we report the third-order NLO features of lissamine green dye using 5 mW power laser with operating wavelength of 650nm. The lissamine green dye is dissolved into various polar solvents such as ethanol, methanol, acetone and DMSO. The closed aperture Z‒scan approach discloses the information about nonlinear refractive index, whereas the open aperture Z‒scan technique provides the information about nonlinear absorption coefficient. The closed aperture curve shows the peak-valley transmittance is the result of self-defocusing nonlinearity and the open aperture transmittance curve switchover from saturable absorption to reverse absorption in high polar solvent due to polarizability and dipole moment. The third-order NLO features such as nonlinear refractive index (n2), nonlinear absorption coefficient (β), real and imaginary features of third-order NLO susceptibility of the dye is calculated to be the order of, 10-7 cm2/W 10-3cm/W, and 10-7 esu respectively. The correlation between solvent polarizability and dipole moment on lissamine green dye is discussed. The results are revealed that the lissamine green dye is a good candidate for NLO applications.

  • Research Article
  • Cite Count Icon 10
  • 10.1089/jop.2023.0056
Efficacy and Safety of the Melanocortin Pan-Agonist PL9643 in a Phase 2 Study of Patients with Dry Eye Disease
  • Nov 1, 2023
  • Journal of Ocular Pharmacology and Therapeutics
  • David Evans + 11 more

Purpose:The melanocortin receptor pan-agonist PL9643, a potential therapy for ocular diseases, was investigated in a phase 2, 12-week study in patients with dry eye disease (DED).Methods:This was a placebo-controlled study evaluating efficacy and safety of thrice-daily PL9643. Placebo (vehicle) was similar to tears. Primary endpoints were intra-patient changes in inferior corneal fluorescein staining and ocular discomfort after 12 weeks. Secondary endpoints were changes in additional DED signs or symptoms. Multiple secondary endpoints were not adjusted for multiplicity. Patients with moderate or severe DED were analyzed in addition to the overall intent-to-treat (ITT) population.Results:In the ITT population (n = 160) the PL9643 group did not demonstrate significant treatment difference versus placebo at week 12/day 85 for the primary endpoints (P > 0.05). In patients with moderate or severe DED (n = 53), PL9643 treatment demonstrated either nominally significant (P < 0.05) or trending (P < 0.1) improvement over placebo in mean change from baseline at week 12/day 85 in several sign endpoints, including fluorescein staining in inferior, superior, corneal sum, and total sum regions; Lissamine Green staining in temporal, nasal, conjunctival sum, and total sum regions; and tear film breakup time. Conjunctival redness also showed (nonsignificant) improvement at week 12/day 85. There were no drug-related adverse events (AEs) and no drug-related discontinuations.Conclusions:PL9643 showed no significant efficacy for the ITT population; however, efficacy results across several signs and symptoms in the subpopulation of moderate to severe DED patients, the low number of ocular AEs, and no tolerability issues suggest that PL9643 shows promise as a therapeutic for DED.Clinical Trial Registration number: NCT04268069.

  • Research Article
  • Cite Count Icon 13
  • 10.1016/j.apsusc.2023.158127
Flower-like magnetite nanoparticles with unfunctionalized surface as an efficient catalyst in photo-Fenton degradation of chemical dyes
  • Jul 27, 2023
  • Applied Surface Science
  • Sylwester Łoński + 5 more

Flower-like magnetite nanoflowers (Fe3O4 NFs) were synthesized in this study using a new, highly scalable, modified co-precipitation method. The heterogeneous photo-Fenton process was optimized for the degradation of Rhodamine B using sodium percarbonate as an alternative source of H2O2. The low dosage of NPs (0.6 mg/ml) can ensure the high Rhodamine B degradation of about 93.6% at pH 4 and sodium percarbonate concentration of 8.3 mg/ml. Studies confirm the high cyclic stability of Fe3O4 NFs and the possibility of using optimized reaction condition in the degradation of Lissamine Green B (97.3%) and Naphthol Green B (61.8%). Moreover, it was confirmed that O2̇− and HO∙ are the primary radicals oxidizing Rhodamine B, while the ultrafast Lissamine Green B degradation corresponds to their oxidation by O2̇−. Finally, surface functionalization was confirmed as one of the most critical parameters in designing catalysts for heterogeneous photo-Fenton processes. The study confirms that in the case of surface functionalization, the degradation of dyes is slowed down (reduction of active sites on the magnetite surface by the organic molecules). Accordingly, the ultrafine, spherical-shaped magnetite nanoparticles functionalized by thrietylene glycol were characterized by above 3 times lower catalytic activity than unfunctionalized Fe3O4 NFs.

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  • Research Article
  • Cite Count Icon 19
  • 10.1186/s12886-023-02931-3
Comparison of mucin levels at the ocular surface of visual display terminal users with and without dry eye disease
  • Apr 28, 2023
  • BMC Ophthalmology
  • Hongyu Duan + 6 more

BackgroundThe long-term use of visual display terminals (VDT) is linked to an increased risk of dry eye disease (DED). Numerous studies have indicated that ocular mucins play a vital role in the pathogenesis of DED. Therefore, we aimed to evaluate (1) whether mRNA levels of membrane-associated mucins (MAMs), including MUC1, MUC4, MUC16, and MUC20, as well as MUC5AC are altered in conjunctival cells of VDT users with and without DED and (2) the relationship between mucin levels and subjective and objective tests of DED in VDT users.MethodsSeventy-nine VDT users were enrolled and divided into DED (n = 53) and control (n = 26) groups. All participants were evaluated for parameters of DED using the Ocular Surface Disease Index (OSDI) questionnaire, tear breakup time (TBUT), corneal fluorescein staining (CFS), lissamine green (LG) staining, and tear meniscus height (TMH). Based on the conjunctival impression cytology (CIC) method, differences in MUC1, MUC4, MUC16, MUC20, and MUC5AC mRNA expression levels were observed between the DED and control groups, and between symptomatic and asymptomatic participants.ResultsThe DED group showed significantly decreased MUC1, MUC16, and MUC20 expressions (all P < 0.05) compared to the control group. In addition, these mucin levels were lower in subjects with frequent ocular symptoms (foreign body sensation, blurred vision and painful or sore eyes) than in asymptomatic participants (all P < 0.05). Correlation analysis revealed that MUC1, MUC16, and MUC20 levels in VDT users were positively correlated with TBUT or TMH, or both. However, no significant relationship was found between MUC4 and MUC5AC levels and the DED parameters.ConclusionVDT users with an increased frequency of ocular discomfort or a diagnosis of DED had a decreased MUC1, MUC16 and MUC20 mRNA expression in their conjunctival cells. MAMs deficiency in the conjunctival epithelium may be one of the mechanisms leading to tear film instability and DED in VDT users.

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