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24 pages, 4279 KB  
Article
Effects of Exposure of PHMG-p, a Humidifier Disinfectant Component, on Eye Dryness: A Study on a Rat Model Based on 1H-NMR Metabolomics
by Jung Dae Lee, Hyang Yeon Kim, Soo Bean Oh, Hyeyoon Goo, Kyong Jin Cho, Gi-Wook Hwang, Suhkmann Kim and Kyu-Bong Kim
Int. J. Mol. Sci. 2025, 26(17), 8660; https://doi.org/10.3390/ijms26178660 - 5 Sep 2025
Viewed by 1115
Abstract
Polyhexamethylene guanidine phosphate (PHMG-p), a widely used disinfectant component in household humidifiers, has been implicated in various health issues, including pulmonary toxicity. Many people use humidifiers to improve dry eye disease (DED). The current study was performed to elucidate the effect of PHMG-p [...] Read more.
Polyhexamethylene guanidine phosphate (PHMG-p), a widely used disinfectant component in household humidifiers, has been implicated in various health issues, including pulmonary toxicity. Many people use humidifiers to improve dry eye disease (DED). The current study was performed to elucidate the effect of PHMG-p on eye dryness in a rat model using metabolomics. Male Sprague Dawley rats were exposed to PHMG-p (0.1% and 0.3%) following a previously established DED induction model using scopolamine hydrobromide and desiccation stress. Ocular surface damage was assessed using corneal fluorescein staining, tear volume measurement, and tear break-up time (TBUT). Plasma and urine samples were analyzed using 1H-NMR-based metabolomics to identify metabolic alterations associated with PHMG-P-p exposure and DED pathogenesis. PHMG-p exposure exacerbated DED symptoms, as evidenced by a significant reduction in tear volume, shorter TBUT, and increased corneal damage compared to the control group. Metabolomic profiling identified distinct metabolic changes in PHMG-p-exposed groups, including alterations in glutamate, glycine, citrate, and succinate metabolism. These metabolic changes correlated with increased levels of inflammatory cytokines such as IL-1β, IL-6, and TNF-α in the corneal and lacrimal gland tissues. Our findings suggest that PHMG-p exposure contributes to DED pathophysiology by inducing metabolic disturbances and inflammatory responses in the ocular surface. This study highlights the need for further investigation into the potential risks of PHMG-p exposure on ocular health and provides novel insights into the metabolic underpinnings of DED. Full article
(This article belongs to the Special Issue Molecular Advances in Dry Eye Syndrome)
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11 pages, 4595 KB  
Article
Histopathologic Evaluation of Corneal Tissue After Adjunctive Rose Bengal Photodynamic Antimicrobial Therapy and Keratoplasty in Advanced Acanthamoeba Keratitis
by Jordan J. Huang, Juan Carlos Navia, Joshua M. Huang, Matthew Camacho, Charissa H. Tan, Paula A. Sepulveda-Beltran, Sara Mustafa, Heather Durkee, Alejandro Arboleda, Mariela C. Aguilar, Darlene Miller, Jean-Marie Parel, Guillermo Amescua, Sander R. Dubovy and Jaime D. Martinez
J. Clin. Med. 2025, 14(17), 6104; https://doi.org/10.3390/jcm14176104 - 29 Aug 2025
Viewed by 694
Abstract
Background/Purpose: To compare the microbiologic and histopathologic features of Acanthamoeba isolates recovered from patients with Acanthamoeba keratitis (AK) who underwent a therapeutic penetrating keratoplasty (TPK), optical penetrating keratoplasty (OPK), or deep anterior lamellar keratoplasty (DALK) after Rose Bengal Photodynamic Antimicrobial Therapy (RB-PDAT). [...] Read more.
Background/Purpose: To compare the microbiologic and histopathologic features of Acanthamoeba isolates recovered from patients with Acanthamoeba keratitis (AK) who underwent a therapeutic penetrating keratoplasty (TPK), optical penetrating keratoplasty (OPK), or deep anterior lamellar keratoplasty (DALK) after Rose Bengal Photodynamic Antimicrobial Therapy (RB-PDAT). Methods: Surgical specimens were stained with hematoxylin, eosin, and Periodic Acid-Schiff stains as per institutional protocol at the University of Miami, Bascom Palmer Eye Institute. Analysis of Acanthamoeba cyst depth, number of cysts, and average corneal thickness was established by light microscopy. Results: Seventeen patients with AK underwent surgical intervention and RB-PDAT. Eight patients underwent a TPK and nine patients underwent an OPK/DALK. In the TPK group, average cyst depth was 42.0 ± 52.5 μm from Descemet’s layer and mean corneal button thickness was 661.7 ± 106.5 μm. Comparatively, in the OPK/DALK group, average cyst depth from Descemet’s layer was 261.7 ± 222.7 μm with a mean corneal button thickness of 474.2 ± 126.6 μm. Conclusions: Acanthamoeba cysts were found to penetrate deeper within the cornea amongst patients that underwent an emergent TPK compared to patients that underwent an elective OPK/DALK. This may suggest an association between Acanthamoeba cyst depth and infection severity and provides valuable clinical insights towards understanding factors such as infection recurrence and resistance to treatment. Full article
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6 pages, 2701 KB  
Case Report
Corneal Edema from Accidental Instillation of Stamper Ink Mistaken for Artificial Tears: A Case Report
by Lily S. Ardiani, Sharita R. Siregar and Iwan Soebijantoro
BioMed 2025, 5(3), 18; https://doi.org/10.3390/biomed5030018 - 22 Aug 2025
Viewed by 761
Abstract
Background: The incidence of chemical ocular trauma after accidentally instilling the “wrong” eyedrops is still frequent, but cases resulting from stamper ink refills are rare. Case Presentation: A 73-year-old man presented to our emergency department with a history of inadvertently instilling stamper ink [...] Read more.
Background: The incidence of chemical ocular trauma after accidentally instilling the “wrong” eyedrops is still frequent, but cases resulting from stamper ink refills are rare. Case Presentation: A 73-year-old man presented to our emergency department with a history of inadvertently instilling stamper ink refill into both eyes (BEs) instead of artificial tears. Immediate irrigation and evaluation were performed. The initial visual acuity (VA) was 0.4 in the right eye (RE) and 0.8 in the left eye (LE). Slit lamp examination showed edema palpebra with periocular blue staining in BEs, chemotic conjunctiva with a much darker color in the RE than the LE, and epithelial defects with a positive fluorescein test in BEs. A diagnosis of bilateral corneal abrasion and chemotic conjunctiva was established. Ten hours after the emergency visit, RE VA decreased to 0.2, and corneal edema was found during the follow-up examination. Medications including levofloxacin antibiotic, sodium hyaluronate, sodium chloride, combined polymyxin sulfate–neomycin sulfate and dexamethasone eyedrops, mefenamic acid, and ascorbic acid tablets were prescribed. The RE corneal edema still occurred, and the endothelial cell count was 1952 and 987 cells/mm2 in the RE and LE at the one-week follow-up. After three weeks, corneal edema had fully resolved, and the VA was 0.4 and 0.8 in the RE and LE, respectively. Conclusions: This case report adds to the spectrum of the continuing problem of chemical ocular trauma after mistakenly instilling the eyedrops. Promoting and changing to different packages for non-ophthalmic products in plastic bottles mimicking eyedroppers is essential to minimize these injuries. Full article
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14 pages, 3376 KB  
Case Report
Clinicopathologic Features, Surgical Treatment, and Pathological Characterization of Canine Dacryops with Different Localization
by Barbara Lamagna, Luigi Navas, Francesco Prisco, Dario Costanza, Valeria Russo, Francesco Lamagna, Cristina Di Palma, Valeria Uccello, Giuseppina Mennonna, Orlando Paciello, Flaviana La Peruta, Giovanni Flauto and Giovanni Della Valle
Vet. Sci. 2025, 12(8), 705; https://doi.org/10.3390/vetsci12080705 - 28 Jul 2025
Viewed by 775
Abstract
Lacrimal cysts (dacryops), which involve lacrimal tissue, are uncommon in dogs with an obscure/unclear pathogenesis. Compared to the current available literature, this report describes the clinicopathologic and immunohistochemical features of two cases of unusual dacryops in brachycephalic dogs. A three-year-old male Cane Corso [...] Read more.
Lacrimal cysts (dacryops), which involve lacrimal tissue, are uncommon in dogs with an obscure/unclear pathogenesis. Compared to the current available literature, this report describes the clinicopathologic and immunohistochemical features of two cases of unusual dacryops in brachycephalic dogs. A three-year-old male Cane Corso was referred with a 1-month history of swelling ventromedial to the left eye associated with blepharospasm and epiphora. Furthermore, a severe lower and upper eyelid entropion and a deep corneal ulcer were present. B-mode ultrasonography and a CT scan revealed a subcutaneous cyst, closely adherent to the maxillary bone. Surgical removal and the correction of entropion were performed. No recurrence and/or complication was detected by seven-year follow-up. Histopathology revealed a cystic structure with single- to double-cell-layered, nonciliated, cuboidal epithelia. Alcian blue stain revealed rare, disseminated goblet cells admixed with epithelial cells. The epithelium was strongly Cytokeratin-positive by immunohistochemistry and appeared lined by several layers of smooth muscle actin (SMA)-positive myoepithelial cells. A 1-year-old male French Bulldog with a 3-month lesion of the third eyelid of the right eye. The lesion (15 mm × 7 mm) beneath the conjunctiva appeared pale-pink, smooth, and multilobulated. Excision was performed by blunt dissection through the conjunctiva on the palpebral surface of the third eyelid. Recovery was uncomplicated, and no recurrence has been noted at three-year follow-up. Cytology of the cystic fluid and histopathology and immunohistochemistry of the cyst wall revealed findings for case 1. To further characterize the SMA-positive spindle cells located directly beneath the cyst-lining epithelium, double-color immunofluorescence for SMA and p63 (a myoepithelial cell marker) was performed on the sample from case 2. The analysis revealed that the SMA-positive cells lacked p63 expression, indicating a non-myoepithelial phenotype. The histological findings in our cases are consistent with previous reports of canine dacryops. The positivity of immunohistochemical staining for SMA in cells directly beneath the epithelium of dacryops in the cases here described in two brachycephalic dogs is consistent with previous reports in dogs and horses but in contrast with a retrospective study about a human dacryops. These results support the conclusion that the pathogenesis of dacryops in dogs should exclude failure of ductular “neuromuscular” contractility. Full article
(This article belongs to the Special Issue Spotlight on Ophthalmologic Pathology in Animals)
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15 pages, 1041 KB  
Article
Clinical Characterization of the Lacrimal Functional Unit in Patients with Chronic Ocular Pain Associated with Dry Eye Disease
by Marta Blanco-Vázquez, Andrea Novo-Diez, Amanda Vázquez, Amalia Enríquez-de-Salamanca, María J. González-García and Margarita Calonge
J. Clin. Med. 2025, 14(15), 5250; https://doi.org/10.3390/jcm14155250 - 24 Jul 2025
Cited by 1 | Viewed by 650
Abstract
Background/Objectives: The purpose of this study was to clinically characterize the lacrimal functional unit (LFU) of patients with chronic ocular pain associated with dry eye disease (DED). Methods: Ninety-three participants were included in this cross-sectional study: 28 patients with chronic ocular [...] Read more.
Background/Objectives: The purpose of this study was to clinically characterize the lacrimal functional unit (LFU) of patients with chronic ocular pain associated with dry eye disease (DED). Methods: Ninety-three participants were included in this cross-sectional study: 28 patients with chronic ocular pain associated with DED (pain-DED), 35 patients with DED but no pain (no pain-DED), and 30 subjects without DED or ocular pain (controls). The following examinations were performed: symptom questionnaires, visual function assessment, tear meniscus, ocular surface evaluation, meibography, corneal sensitivity, Schirmer test, and in vivo corneal confocal microscopy. Results: Both DED groups presented increased DED-related symptoms (p < 0.001), corneal staining (p < 0.001), Meibomian gland loss (p < 0.010), and dendritic cell density (p < 0.001) compared with controls. Comparing both DED groups, the pain-DED group showed higher DED-related symptoms (p < 0.002) and increased microneuroma density (p < 0.001). Additionally, significant positive correlations were observed between symptom questionnaires and corneal staining (vs. OSDI: r = 0.514, p < 0.001; vs. m-SIDEQ: r = 0.504, p < 0.001; vs. NRS: r = 0.361, p < 0.001; vs. WBFPRS: r = 0.317, p = 0.002), dendritic cell density (vs. OSDI: r = 0.429, p < 0.001; vs. m-SIDEQ: r = 0.440, p < 0.001), and microneuroma density (vs. NRS: r = 0.405, p < 0.001; vs. WBFPRS: r = 0.416, p < 0.001). Conclusions: Differences in the LFU, especially in the morphology of sub-basal corneal nerves, are related to the presence of DED and chronic ocular pain and, along with ocular clinical questionnaires, can help phenotype these patients. Full article
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12 pages, 557 KB  
Article
Advancing Diagnostics with Semi-Automatic Tear Meniscus Central Area Measurement for Aqueous Deficient Dry Eye Discrimination
by Hugo Pena-Verdeal, Jacobo Garcia-Queiruga, Belen Sabucedo-Villamarin, Carlos Garcia-Resua, Maria J. Giraldez and Eva Yebra-Pimentel
Medicina 2025, 61(8), 1322; https://doi.org/10.3390/medicina61081322 - 22 Jul 2025
Viewed by 473
Abstract
Background and Objectives: To clinically validate a semi-automatic measurement of Tear Meniscus Central Area (TMCA) to differentiate between Non-Aqueous Deficient Dry Eye (Non-ADDE) and Aqueous Deficient Dry Eye (ADDE) patients. Materials and Methods: 120 volunteer participants were included in the study. Following [...] Read more.
Background and Objectives: To clinically validate a semi-automatic measurement of Tear Meniscus Central Area (TMCA) to differentiate between Non-Aqueous Deficient Dry Eye (Non-ADDE) and Aqueous Deficient Dry Eye (ADDE) patients. Materials and Methods: 120 volunteer participants were included in the study. Following TFOS DEWS II diagnostic criteria, a battery of tests was conducted for dry eye diagnosis: Ocular Surface Disease Index questionnaire, tear film osmolarity, tear film break-up time, and corneal staining. Additionally, lower tear meniscus videos were captured with Tearscope illumination and, separately, with fluorescein using slit-lamp blue light and a yellow filter. Tear meniscus height was measured from Tearscope videos to differentiate Non-ADDE from ADDE participants, while TMCA was obtained from fluorescein videos. Both parameters were analyzed using the open-source software NIH ImageJ. Results: Receiver Operating Characteristics analysis showed that semi-automatic TMCA evaluation had significant diagnostic capability to differentiate between Non-ADDE and ADDE participants, with an optimal cut-off value to differentiate between the two groups of 54.62 mm2 (Area Under the Curve = 0.714 ± 0.051, p < 0.001; specificity: 71.7%; sensitivity: 68.9%). Conclusions: The semi-automatic TMCA evaluation showed preliminary valuable results as a diagnostic tool for distinguishing between ADDE and Non-ADDE individuals. Full article
(This article belongs to the Special Issue Advances in Diagnosis and Therapies of Ocular Diseases)
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12 pages, 376 KB  
Article
Insulin Nanoemulsion Eye Drops for the Treatment of Dry Eye Disease in Sjögren’s Disease: A Randomized Clinical Trial Phase I/II
by Mateus Maia Marzola, Diego Rocha Gutierrez, Beatriz Carneiro Cintra, Adriana de Andrade Batista Murashima, Luciana Facco Dalmolin, Denny Marcos Garcia, Renata Fonseca Vianna Lopez, Fabiola Reis Oliveira and Eduardo Melani Rocha
Vision 2025, 9(3), 54; https://doi.org/10.3390/vision9030054 - 9 Jul 2025
Viewed by 1372
Abstract
Dry eye disease (DED) is a hallmark of primary Sjögren’s disease (SjD) and often resists conventional treatments like lubricant eye drops. Insulin nanoemulsions offer a potential solution by improving drug penetration and retention on the ocular surface. In animal models, insulin has shown [...] Read more.
Dry eye disease (DED) is a hallmark of primary Sjögren’s disease (SjD) and often resists conventional treatments like lubricant eye drops. Insulin nanoemulsions offer a potential solution by improving drug penetration and retention on the ocular surface. In animal models, insulin has shown benefits in promoting tear secretion and corneal healing. This study evaluated the safety and efficacy of insulin nanoemulsion eye drops (20 IU/mL, three times daily for 30 days) in patients with SjD. Thirty-two patients were randomized in a double-masked design to receive either insulin or placebo drops. Symptoms (assessed by OSDI questionnaire) and objective measures (tear film breakup time, corneal and conjunctival staining, and Schirmer Test) were recorded at baseline, after 4 weeks of treatment, and at a 4-week follow-up. Twenty-three participants completed the study. Both groups showed significant improvement in symptoms and objective signs after treatment (p < 0.05), but no significant differences were found between the insulin and placebo groups. No clinically relevant adverse effects were reported. Insulin nanoemulsion eye drops are safe for SjD patients, but their therapeutic advantage remains unclear. Further studies with larger samples, extended follow-up, and dose adjustments are needed to better understand their potential. Full article
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19 pages, 403 KB  
Article
Long-Term Evolution of Chronic Neuropathic Ocular Pain and Dry Eye Following Corneal Refractive Surgery
by Cristina Valencia-Sandonís, Amanda Vázquez, Laura Valencia-Nieto, Elena Martínez-Plaza, Marta Blanco-Vázquez, Eva M. Sobas, Margarita Calonge, Enrique Ortega, Amalia Enríquez-de-Salamanca and María J. González-García
J. Clin. Med. 2025, 14(13), 4406; https://doi.org/10.3390/jcm14134406 - 20 Jun 2025
Cited by 1 | Viewed by 1876
Abstract
Background/Objectives: Chronic neuropathic ocular pain (NOP) can manifest concurrently with dry eye (DE) symptoms following ocular surgical procedures. Due to its low prevalence, NOP remains an underrecognized and underdiagnosed postoperative complication, leading to suboptimal management. This study evaluated the long-term evolution of [...] Read more.
Background/Objectives: Chronic neuropathic ocular pain (NOP) can manifest concurrently with dry eye (DE) symptoms following ocular surgical procedures. Due to its low prevalence, NOP remains an underrecognized and underdiagnosed postoperative complication, leading to suboptimal management. This study evaluated the long-term evolution of symptoms, signs, and tear biomarkers in patients with NOP and DE after corneal refractive surgery (RS). Methods: Patients with chronic NOP and persistent DE-related symptoms after corneal RS were assessed in two visits (V1 and V2), at least two years apart. Symptoms (DE, pain, anxiety, and depression) were measured with specific questionnaires. Clinical examination included a slit-lamp ocular surface evaluation, corneal sensitivity measurement, and subbasal corneal nerve plexus evaluation. Basal tear samples were collected, and a 20-plex cytokine panel and Substance P (SP) were assayed. Results: Twenty-three patients (35.57 ± 8.43 years) were included, with a mean time between visits of 4.83 ± 1.10 years. DE symptoms, measured with the Ocular Surface Disease Index questionnaire, improved at V2 (p < 0.001), along with a reduction in anxiety and depression levels, measured with the Hospital Anxiety and Depression Scale (p = 0.027). Corneal staining also decreased (p < 0.001), while subbasal nerve plexus parameters and corneal sensitivity remained unchanged. Tear analysis revealed increased concentrations of fractalkine/CX3CL1 (p = 0.039), interleukin (IL)-1 receptor antagonist (Ra) (p = 0.025), IL-10 (p = 0.002), and SP (p < 0.001). Conclusions: Symptom improvement may result from better control of underlying pathologies or natural disease progression. However, the increased levels of SP and fractalkine/CX3CL1 suggest sustained neurogenic inflammation, while elevated IL-1Ra and IL-10 indicate a potential compensatory anti-inflammatory response. Full article
(This article belongs to the Special Issue Advances in Dry Eye Disease Treatment: 2nd Edition)
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21 pages, 4687 KB  
Article
The Ability of Bacteriophages to Reduce Biofilms Produced by Pseudomonas aeruginosa Isolated from Corneal Infections
by Kuma Diriba Urgeya, Dinesh Subedi, Naresh Kumar and Mark Willcox
Antibiotics 2025, 14(7), 629; https://doi.org/10.3390/antibiotics14070629 - 20 Jun 2025
Viewed by 2361
Abstract
Pseudomonas aeruginosa (P. aeruginosa) is a common antibiotic-resistant pathogen, posing significant public health threats worldwide. It is a major cause of ocular infections, mostly linked to contact lens wear. P. aeruginosa often produces biofilm during infections, and these are also associated [...] Read more.
Pseudomonas aeruginosa (P. aeruginosa) is a common antibiotic-resistant pathogen, posing significant public health threats worldwide. It is a major cause of ocular infections, mostly linked to contact lens wear. P. aeruginosa often produces biofilm during infections, and these are also associated with antibiotic resistance. Bacteriophage (phage) therapy is emerging as a promising approach for treating multidrug-resistant P. aeruginosa. Objective: This study aimed to assess the antibiofilm effects of six phages against P. aeruginosa biofilms isolated from patients with corneal infections. Method: This study examined P. aeruginosa strains for their ability to form biofilms using crystal violet assay. Six P. aeruginosa bacteriophages (DiSu1 to DiSu6) were used, which were isolated from sewage water in Melbourne, Australia. Spot tests were used to assess phage sensitivity. The effect of phages against P. aeruginosa strains was determined using time–kill assay and efficiency of plating. The ability of phage to inhibit biofilm formation over 24 h or reduce preformed biofilms was also studied and confirmed using confocal laser scanning microscopy with Live/Dead staining. Result: After 24 h of incubation, all tested P. aeruginosa strains formed moderate to strong biofilms. All P. aeruginosa strains were sensitive to at least four of the six phages. The highest level of bacterial growth inhibition in the liquid infection model was observed when phages were applied at a multiplicity of infection (MOI) of 100. Certain bacteria/phage combinations were able to inhibit biofilm formation over 24 h, with the combination of strain PA235 and phage DiSu3 producing the highest inhibition (83%) at a MOI of 100. This was followed by the combinations of PA223/DiSu3 (56%), and PA225/DiSu5 (52%). For the reduction in preformed biofilms, the best combinations were PA235 (90%), PA221 (61%), and PA213 and PA225 (57% each), all with DiSu3 after 3 h. However, exposing the biofilm with phages for over 24 h appeared to promote phage resistance as there was evidence of biofilm growth, with the only combination still showing a significant reduction being PA221/DiSu3 (58%) at MOI of 100. Conclusions: This study showed that the effect of phages against P. aeruginosa is concentration (MOI) dependent. Phages at higher MOI have the ability to disrupt, inhibit, and reduce P. aeruginosa biofilms. However, prolonged exposure of the biofilm with phages appeared to promote phage resistance. To enhance phage efficacy and address this form of resistance, further studies utilizing phage cocktails or a combination of phages and antibiotics is warranted. Full article
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12 pages, 2843 KB  
Article
Effect of Strabismus Surgery on Meibomian Glands, Ocular Surface Parameters, and Conjunctival Impression Cytology
by Şenol Sabancı, Canan Sadullahoğlu, Sibel Yavuz, Mehmet Fatih Küçük, Esra Kızıldağ Özbay, Muhammet Kazım Erol and Berna Doğan
Diagnostics 2025, 15(10), 1291; https://doi.org/10.3390/diagnostics15101291 - 21 May 2025
Viewed by 865
Abstract
Background/Objectives: To investigate the effect of strabismus surgery on ocular surface parameters, meibomian glands, and conjunctival impression cytology. Methods: Preoperative and postoperative (10th day, first month, and third month) tear break-up time (TBUT) tests, Schirmer 1 tests, corneal staining scores (CSS), [...] Read more.
Background/Objectives: To investigate the effect of strabismus surgery on ocular surface parameters, meibomian glands, and conjunctival impression cytology. Methods: Preoperative and postoperative (10th day, first month, and third month) tear break-up time (TBUT) tests, Schirmer 1 tests, corneal staining scores (CSS), meibomian gland (MG) loss rates, ocular surface disease index (OSDI) scores, and conjunctival impression cytology (IC) results of 30 patients who underwent strabismus surgery were compared. Results: Significant differences were found between preoperative TBUT test results and those evaluated on the postoperative 10th day and at the postoperative first month (p < 0.0001 for both). There were also significant differences between the preoperative and postoperative first- and third-month Schirmer 1 test results (p = 0.02 and p < 0.0001, respectively). Furthermore, mean OSDI scores significantly differed between preoperative and postoperative 10th-day measurements (p < 0.0001). The mean postoperative 10th-day CSS was found to be significantly higher than the preoperative mean CSS (p < 0.0001). The stages in preoperative conjunctival IC samples were found to be significantly lower than those evaluated at all postoperative times (p < 0.0001 for all). Significant differences were observed between the preoperative lower eyelid MG loss rate and all postoperative MG loss rates (p < 0.0001 for the 10th day and first month and p < 0.001 for the third month). Lastly, the preoperative upper eyelid MG loss rate significantly differed from all postoperative MG loss rates (p < 0.0001 for the 10th day, p < 0.003 for the first month, and p < 0.0001 for the third month). Conclusions: We observed changes indicative of dry eye in the mean OSDI score, TBUT, Schirmer 1 test, MG loss rates, and conjunctival IC findings up to the postoperative third month in patients who underwent strabismus surgery. Therefore, we believe that patients undergoing strabismus surgery should be followed up for ocular surface diseases, particularly dry eye. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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21 pages, 4865 KB  
Article
Therapeutic Potential of Umbilical Cord MSC-Derived Exosomes in a Severe Dry Eye Rat Model: Enhancing Corneal Protection and Modulating Inflammation
by Sze-Min Chan, Chris Tsai, Tai-Ping Lee, Zih-Rou Huang, Wei-Hsiang Huang and Chung-Tien Lin
Biomedicines 2025, 13(5), 1174; https://doi.org/10.3390/biomedicines13051174 - 11 May 2025
Cited by 1 | Viewed by 2016
Abstract
Background/Objectives: Dry eye disease (DED) is a multifactorial inflammatory disease that disrupts the ocular surface, causing tear film instability, epithelial damage, and chronic inflammation. Mesenchymal stem cell-derived exosomes (MSC-exos) are promising therapeutics with immunomodulatory and regenerative properties. This study investigates the therapeutic [...] Read more.
Background/Objectives: Dry eye disease (DED) is a multifactorial inflammatory disease that disrupts the ocular surface, causing tear film instability, epithelial damage, and chronic inflammation. Mesenchymal stem cell-derived exosomes (MSC-exos) are promising therapeutics with immunomodulatory and regenerative properties. This study investigates the therapeutic effects of umbilical cord MSC-derived exosomes (UCMSC-exos) in a severe dry eye model, induced by a surgical resection of the infra-orbital (ILG) and extra-orbital lacrimal gland (ELG) in rats. Methods: Clinical evaluations, including tear volume measurement, slit lamp biomicroscopy, fluorescein staining, and spectral domain optical coherence tomography (SD-OCT), were performed to assess corneal neovascularization, corneal abrasion, and epithelial/stromal thickness. Histopathological analysis, immunohistochemistry, and mRNA gene expression were conducted to evaluate corneal tissue changes and inflammatory marker expression. Results: The results show that the treatment group exhibited significantly reduced corneal neovascularization compared to the control group (p = 0.030). During the first month, the Exo group also had a significantly lower corneal fluorescein staining area (p = 0.032), suggesting accelerated wound healing. SD-OCT analysis revealed that the corneal epithelial thickness in the treatment group was closer to normal levels compared to the control group (p = 0.02 and p = 0.006, respectively). UCMSC-exos treatment also modulated the expression of α-SMA and apoptosis in the cornea. Additionally, the gene expression of inflammatory cytokines (IL-1β and TNF-α) were downregulated. Conclusions: These findings suggest that MSC-exosome therapy offers a novel, cell-free regenerative approach for managing severe DED, modulating inflammatory response. Full article
(This article belongs to the Section Cell Biology and Pathology)
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16 pages, 3287 KB  
Article
Evaluating Magnetic Stimulation as an Innovative Approach for Treating Dry Eye Disease: An Initial Safety and Efficacy Study
by Hadas Ben-Eli, Shimon Perelman, Denise Wajnsztajn and Abraham Solomon
Biomedicines 2025, 13(5), 1064; https://doi.org/10.3390/biomedicines13051064 - 28 Apr 2025
Viewed by 985
Abstract
Objective: The aim of this study was to assess the safety and preliminary efficacy of repetitive magnetic stimulation (RMS) as a treatment intervention for dry eye disease (DED), focusing on symptom reduction. Methodology: This investigation involved 22 adult participants (85% females, aged between [...] Read more.
Objective: The aim of this study was to assess the safety and preliminary efficacy of repetitive magnetic stimulation (RMS) as a treatment intervention for dry eye disease (DED), focusing on symptom reduction. Methodology: This investigation involved 22 adult participants (85% females, aged between 22 and 79 years) diagnosed with moderate-to-severe DED. These individuals were subjected to RMS treatment targeting one or both eyes using the VIVEYE-Ocular Magnetic Neurostimulation System version 1.0 (Epitech-Mag LTD; National Institute of Health (NIH) clinical trials registry #NCT03012698). A placebo-controlled group was also included for comparative analysis, with all subjects being monitored over a three-month period. The evaluation of safety encompassed monitoring changes in best corrected visual acuity, ocular pathology, and the reporting of adverse events. Participant tolerance was gauged through questionnaires, measurements of intraocular pressure (IOP), Schirmer’s test, and vital signs. The efficacy of the treatment was assessed by comparing pre- and post-treatment scores for fluorescein staining (according to National Eye Institute (NEI) grading) and patient-reported outcomes. Results: No statistically significant changes were found in visual acuity, IOP, or Schirmer’s test results between the RMS-treated and control groups (p < 0.05), indicating that RMS does not negatively impact these ocular functions. However, RMS treatment was associated with improved tear film stability (p = 0.19 vs. p = 0.04) and corneal health (p = 0.52 vs. p = 0.004), with no improvements in the control group. Initial symptom improvement was observed in both RMS-treated and placebo groups (p = 0.007 vs. p = 0.008), suggesting a potential therapeutic benefit of RMS for ocular surface conditions beyond a placebo effect. Conclusions: This study presents RMS as a promising therapeutic approach for DED, highlighting its potential to promote corneal epithelial repair, enhance tear film stability, and improve patient-reported symptoms without negatively impacting IOP, visual acuity, or tear production. This confirms the safety and suggests the efficacy of RMS therapy for dry eye conditions. Full article
(This article belongs to the Special Issue Recent Research on Dry Eye)
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10 pages, 1976 KB  
Article
In Vitro Toxicity of Cetalkonium Chloride on Corneal Epithelial Cells
by Joo-Hee Park and Choul Yong Park
Pharmaceutics 2025, 17(4), 522; https://doi.org/10.3390/pharmaceutics17040522 - 16 Apr 2025
Viewed by 1204
Abstract
Objective: To investigate the toxicity of cetalkonium chloride (CKC) on primary cultured human corneal epithelial cells (HCECs). Methods: HCECs were subjected to various concentrations (0.03125 × 10−4 to 2.0 × 10−4% (w/v)) of CKC for durations [...] Read more.
Objective: To investigate the toxicity of cetalkonium chloride (CKC) on primary cultured human corneal epithelial cells (HCECs). Methods: HCECs were subjected to various concentrations (0.03125 × 10−4 to 2.0 × 10−4% (w/v)) of CKC for durations ranging from 24 to 72 h. Cell viability was evaluated using the CCK-8 kit along with live and dead cell staining. Intracellular reactive oxygen species (ROS) levels were measured 20 min following CKC exposure. Observations of changes in cell morphology, cytoplasmic actin filaments, and mitochondrial distribution were conducted using immunocytochemistry and MitoTracker assays. Protein expression levels related to cell survival pathways, including mTOR, ERK, Akt, Bcl-xL, and BAX, were examined via Western blot analysis. Results: CKC exhibited dose-dependent toxicity in HCECs. Exposure to CKC concentrations below 0.125 × 10−4% resulted in no significant decrease in HCEC viability for up to 72 h. Conversely, exposure to CKC at concentrations of 1.0 × 10−4% or higher led to significantly decreased HCEC viability. Following exposure to higher concentrations of CKC, elevated levels of intracellular ROS and LDH release were observed. This toxicity was further characterized by decreased levels of phosphorylated mTOR, phosphorylated Akt, phosphorylated ERK, and Bcl-xL, as well as an increase in BAX expression. As the CKC concentration increased, HCECs decreased in size, and mitochondria displayed a loss of characteristic punctate staining. Conclusions: Our findings indicated that exposure to CKC caused significant toxicity in HCECs, which varied with concentration and duration of exposure. This toxicity was associated with an increase in ROS, mitochondrial alterations, and a decline in activity of the cell survival pathways. Full article
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16 pages, 4272 KB  
Article
Characterization of Individuals with High-Frequency Artificial Tear Supplement Use
by Wan-Lin Wu and Shu-Wen Chang
J. Clin. Med. 2025, 14(8), 2694; https://doi.org/10.3390/jcm14082694 - 15 Apr 2025
Viewed by 768
Abstract
Objectives: We aimed to investigate dry eye parameters as potential predisposing factors and estimate the prevalence of high-frequency topical eye drop usage. Methods: A total of 5594 dry eye patients treated between November 2015 and June 2022 were included. High users [...] Read more.
Objectives: We aimed to investigate dry eye parameters as potential predisposing factors and estimate the prevalence of high-frequency topical eye drop usage. Methods: A total of 5594 dry eye patients treated between November 2015 and June 2022 were included. High users (n = 180) were those who applied at least one artificial tear drop per hour, whereas those who used artificial tears fewer than four times daily were classified as low users (n = 5414). Differences in self-reported symptoms (OSDI, SPEED questionnaires) and tear-related parameters, including severity of corneal staining (SPK), fluorescein tear-film break-up time (FTBUT), lipid layer thickness (LLT), number of expressible meibomian glands (MGE), meiboscale, and blink patterns, were assessed. Subsequent follow-up comprehensive dry eye assessments were performed at 3 months. Results: There was no difference in age or sex between high users and low users (p = 0.075 and 0.508, respectively). High users had significantly higher symptom scores (p < 0.001), more total blinks (p = 0.001), lower Schirmer scores (p < 0.001), higher SPK grades (p < 0.001), shorter FTBUT (p = 0.010), and higher limbal redness scores (p = 0.002). However, there were no differences in the LLT, MGE, or meiboscale. The compliance with follow-up examinations at 3 months was significantly greater for the high users (p < 0.001). Patients with OSDI scores > 40, SPEED scores > 12, Schirmer scores ≤ 3 mm, and higher compliance with follow-up examinations had odds ratios of 4.0, 3.3, 1.7, and 4.1, respectively, for being high users (95% confidence intervals = 2.8–5.8, 2.4–4.7, 1.2–2.3 and 2.7–5.2, respectively). Among the high users, reducing topical drops significantly decreased the SPEED and OSDI scores, except for the environmental trigger factor in the OSDI questionnaire. During long-term follow-up, 1.1% of low users and 15.4% of high users received cyclosporine treatment (odds ratio 16.4, p < 0.001). Conclusions: OSDI scores > 40, SPEED scores > 12, and Schirmer scores ≤ 3 mm were associated with high-frequency eye drop usage, which accounted for 3.2% of moderate to severe dry eye patients. Susceptibility to environmental triggers could represent hyperalgesia/allodynia in high users. High users have a higher need for cyclosporine treatment. Full article
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16 pages, 6744 KB  
Article
Effect of Decorin and Aligned Collagen Fibril Topography on TGF-β1 Activation of Corneal Keratocytes
by Nathaniel S. Tjahjono, Divya Subramanian, Tarik Z. Shihabeddin, Hudson D. Hicks, Victor D. Varner, W. Matthew Petroll and David W. Schmidtke
Bioengineering 2025, 12(3), 259; https://doi.org/10.3390/bioengineering12030259 - 5 Mar 2025
Cited by 1 | Viewed by 1394
Abstract
During corneal wound healing, transforming growth factor-beta 1 (TGF-β1) causes differentiation of quiescent keratocytes into myofibroblasts. Decorin has been investigated as a promising anti-fibrotic therapeutic for corneal healing due to its interaction with TGF-β1, collagen, and cell surface receptors. In this study, a [...] Read more.
During corneal wound healing, transforming growth factor-beta 1 (TGF-β1) causes differentiation of quiescent keratocytes into myofibroblasts. Decorin has been investigated as a promising anti-fibrotic therapeutic for corneal healing due to its interaction with TGF-β1, collagen, and cell surface receptors. In this study, a novel microfluidic method for coating aligned collagen fibrils with decorin was developed to mimic the presence of decorin within the corneal stroma. Decorin was found to bind selectively to collagen and remained bound for at least five days. To investigate the effects of decorin coatings on keratocyte activation, primary rabbit keratocytes were cultured in the presence of TGF-β1 for 5 days on substrates with or without decorin and stained for α-smooth muscle actin (α-SMA). The expression of α-SMA was reduced by similar amounts on monomeric collagen (40%), random collagen fibrils (32%), and aligned collagen fibrils (32%) coated with decorin as controls. However, α-SMA expression was differentially expressed between the collagen substrates not coated with decorin, with significantly lower expression on uncoated aligned collagen fibrils compared to uncoated collagen monomers. Addition of decorin directly to culture media, had a limited effect on reducing myofibroblast differentiation. Taken together, these results demonstrate the importance of topography and ECM composition on keratocyte activation. Full article
(This article belongs to the Special Issue Bioengineering and the Eye—2nd Edition)
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