bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ocular lichen planus: An unusual occurence
Authors: Ferrando Sergio Obiol , Ortega Aranzazu Caro , García Amparo Lanuza , de Lara Sánchez Sofía Sánchez , Nadal Andrea Català , Duch‐Samper Antonio , Bouchoutrouch Sarra , Serrano Diego 
Published: January 2025

Aims/Purpose: Lichen planus (LP) is an inflammatory disease of autoimmune etiology that primarily affects skin and mucous membranes. Its prevalence varies between 0.07% and 0.84%. The most frequently affected area is the oral mucosa, followed by the genital area. Ocular involvement is extremely rare in the scientific literature. Most cases of ocular LP manifest as chronic cicatrizing conjunctivitis. Chronic inflammation leads to subepithelial fibrosis, shortening of the fornix and symblepharon with irreversible fibrotic changes. Compared to conjunctival LP, corneal involvement is much less frequent.Methods: A 79‐year‐old male consulted with loss of visual acuity in both eyes in the last two months, with greater loss in the right eye. At the initial visit, a maximum corrected visual acuity of 0.2 in the right eye and counting fingers at 2 meters in the left eye was observed. Biomicroscopic examination of both eyes showed a 360° corneal pannus, a very short tear breakup time, erythema of upper portion and lower portion of the eyelids, severe conjunctival hyperemia, subepithelial fibrosis with shortening of the fornix and presence of inferior symblepharon in both eyes. A scheduled conjunctival biopsy was performed two days after the first visit on the nasal and temporal side of both eyes. Direct immunofluorescence (DIF) results showed linear fibrinogen deposition along the basement membrane consistent with the diagnosis of ocular LP.Results: After the diagnosis the patient was prescribed tacrolimus 0.03% eye drops every 12 hours and intense lubrication of the ocular surface with daily topical artificial tears and nightly ointment.Conclusions: Ocular LP is an extremely rare disease, with few cases described in the literature. The most common form of ocular clinical presentation is conjunctival, with corneal involvement being extremely infrequent. Treatment is based on topical and/or systemic immunomodulatory drugs.References
Mohebbi M, Mirghorbani M, Banafshe Afshan A, Towfighi M. Lichen planus in ocular surface: Major presentations and treatments. Ocul Immunol Inflamm. 2019; 27(6): 987–94.
Safadi M, Viglione M, Zahner S. Ocular lichen planus: An unusual presentation, its treatment, and review of the literature. JAAD Case Rep. 2021; 14: 4–6.
Possible necrotizing scleritis and non‐infectious vitritis following intravitreal injection of bevacizumab
Authors: Outeiriño Patricia Roig , del Mar Esteban Ortega Maria , Martín Sergio Pernas , de Lázaro Alejandra Antón Guzmán , Hernández Eduardo Conesa , Carretero Manuel Moriche 
Published: January 2025

Aims/Purpose: This case report describes possible necrotizing scleritis and non‐infectious vitritis in the right eye following intravitreal injections of bevacizumab for the treatment of postsurgical cystic macular edema, highlighting the potential immune‐mediated adverse reactions associated with the intravitreal treatment.Methods: An ophthalmological examination was performed along with laboratory and imaging tests to diagnose the patient.Results: After the first injection, the patient developed intense ocular redness, scleral thinning, and pancorneal punctate keratitis, with possible necrotizing scleritis suspected. Treatment was iniciated with a positive progress, however, after resuming the treatment with bevacizumab due to persistence of macular edema, the patient experienced blurred vision and photophobia, and mild vitritis was observed during the examination. Topical treatment produced rapid improvement, but due to suspicion of an immune‐mediated reaction, bevacizumab was discontinued. Alternative treatments were considered, including other anti‐VEGF agents and topical anti‐inflammatory medications.Conclusions: Although necrotizing scleritis is not described as a possible adverse reaction to treatment with intravitreal bevacizumab, its association with another immune‐mediated reaction that also coincides in time with the treatment suggests a possible causal relationship. This case highlights the importance of recognizing and managing rare immune‐related adverse reactions to intravitreal treatments, emphasizing the need for alternative therapies that minimize risks to the patient.
The relationship between corneal nerve density and corneal dendritic cells in patients with type 2 diabetes macular edema
Authors: Filipek Ania Cikowska , Lagali Neil , Viberg Andreas , Johannesson Gauti , Byström Berit 
Published: January 2025

Aims/Purpose: The purpose of this study is to examine a possible correlation of diabetic macular edema (DME) with changes in the anterior segment, focusing on corneal subbasal nerve fibers and the density of corneal inflammatory cells in diabetes type 2.Methods: Cross‐sectional examination of 30 subjects with type 2 diabetes and DME, and 30 volunteers without diabetes using corneal confocal microscope the same morning as their retinal status were checked. Quantitative measurements of corneal subbasal nerve fibers were made using semi‐automated tracing software. An average corneal nerve fiber length, defined as total length of nerve fibers and nerve branches within a frame (mm/mm2), from every image was quantified. The density of activated and non‐activated dendritic cells in the same corneal layer and same images were additionally identified and quantified.Results: Preliminary results from 15 subjects with DME and 15 controls showed a trend towards reduced nerve fiber density especially in the whorl region of the corneas, in the DME group. On the contrary, preliminary results did not show a clear difference in the amount of dendritic cells when comparing the groups.Conclusions: Preliminary results suggest a novel connection between the diabetic status of the eye with DME and the corneal subbasal nerve fiber layer especially in the whorl region of the cornea. A reduced density of nerves was apparent in the DME group. More cases will be analyzed to study the relationships in more detail, which might provide a means to monitor the inflammatory status of DME.
Microbial keratitis in a tertiary hospital in Ireland
Authors: Hegazy Esraa , Fauzi Muhammad Yusuf Bin Mohd , Houlihan Elaine , Gallagher David , Quill Barry , Power William , Knowles Susan , Murphy Conor 
Published: January 2025

Aims/Purpose: The aim of this study is to describe trends in the pathogens and antimicrobial resistance isolated from corneal scrapings in a Tertiary Eye Care Centre in Ireland over 10 years.Methods: Electronic health records of corneal scrapings sent over the period 01.1.2014 until the 31.12.2023 were retrieved. These included positive and negative scrapes, the pathogens isolated as well as antimicrobial sensitivity and resistance.Results: Overall, 1,291 patients underwent corneal scrapings during this time period. Negative corneal scrapings were found in 52.7% (n = 681) of eyes and 47.3% (n = 610) of eyes yielded positive results. Out of the positive corneal scrapings, 56 had 2 organisms isolated and 6 had 3 organisms isolated. A total of 672 organisms were isolated. Bacteria were isolated in 91.8% (n = 617) of scrapings and fungi were isolated in 8.2% (n = 55) of scrapings. The most common bacterial organisms isolated were coagulase‐negative Staphylococcus (21.8%). Staphylococcus aureus was found in 123 eyes (19.9%), 7 of these were methicillin‐resistant Staphylococcus aureus. This was followed by Moraxella (15.7%), Pseudomonas aeruginosa (15.6%), Streptococcus pneumoniae (6.6%), Corynebacterium (3.8%) and Serratia (3.7%). Of the positive scrapings for fungal infection, Fusarium was the most common fungi isolated (38.2%). Candida was second (25.5%) and Aspergillus (9%) was third. Trends in antimicrobial resistance remained stable over the 10 years. Chloramphenicol drops were sensitive in Staphylococcus aureus (95%), Moraxella (98%) and Streptococcus pneumoniae (100%). Topical ofloxacin was sensitive in Pseudomonas aeruginosa (100%) and in Moraxella (88%). Moxifloxacin was sensitive in Streptococcus pneumoniae (100%), Staphylococcus aureus (92%) and Corynebacterium (87.5%).Fusarium species were sensitive to Natamycin (90%) and Amphotericin B (66%). Candida species were sensitive to Amphotericin B (100%) and Fluconazole (100%). Aspergillus was sensitive to Amphotericin B (100%).Conclusions: Bacterial microorganisms accounted for the majority of isolates from corneal scrapings. It is important to be aware of the most common pathogens associated with microbial keratitis including corresponding antibiotic sensitivity. Rates of microbial keratitis infections did not change over time.
The role of substance P in maintaining corneal innervation and ocular surface homeostasis
Authors: Suanno Giuseppe , Fonteyne Philippe , Bartolomeo Nicolò , De Micheli Massimo , Bandello Francesco , Ferrari Giulio 
Published: January 2025

Aims/Purpose: To assess the role of Substance P (SP) in maintaining corneal nerve homeostasis. Specifically, we aimed to study how SP impacts sensory nerve regeneration and, in turn, ocular surface physiology.Methods: This study included eight‐week‐old mice C57BL6/N (WT mice) and Tac1‐deficient B6.Cg‐Tac1tm1Bbm/J (SP‐KO mice). Corneal denervation was achieved by means of central trephination. Mice were followed up to six weeks after denervation, corneal sensitivity, nociception, corneal fluorescein staining were measured at different time points. After sacrifice, corneas were collected and immuno‐stained for beta‐III tubulin, as a marker of corneal nerve density.Results: SP‐KO mice showed lower beta‐III tubulin staining than WT mice at the baseline (p < 0.01). After trephination, beta‐III tubulin‐positive fibers were significantly reduced in both groups (p < 0.0001) and they were restored in WT mice six weeks after trephination. Similarly, corneal sensitivity was significantly reduced after trephination in both groups (p < 0.0001), and returned to normal levels after 6 weeks in WT mice. Nociception was significantly lower in SP‐KO versus WT mice up to 5 weeks after trephination. Interestingly, punctate keratopathy scores following trephination were higher in SP‐KO mice versus controls (p < 0.0001).Conclusions: Our findings show that trephination significantly affects ocular surface integrity, pain response/sensitivity and corneal nerve regeneration. SP may have an impact on corneal nerve regeneration following trephination.
4 mm Descemetorhexis and anterior lens capsule graft versus descemet striping only: A preclinical study
Authors: Goin Paul , Louise Parveau , Poinard Sylvain , Oliver Dorado Cortez , He Zhiguo , Philippe Gain , Thuret Gilles 
Published: January 2025

Aims/Purpose: Fuchs endothelial corneal dystrophy is currently the main indication for keratoplasty. Alternatively, a localized 4mm Descemet Stripping Only (DSO) has been proposed to treat selected patients with a sufficient peripheral endothelial reserve (1,2). Visual recovery is generally longer than after keratoplasty but no immunosuppressive treatment is needed (3). The anterior lens capsule (ALC) can be used as a support for the culture of corneal endothelial cells (CECs)(4). Their migration is facilitated by the presence of a basal membrane. Aim: to assess the migration capacity of CECs with and without the addition of an ACL disc after a 4mm Descemetorhexis in an ex vivo modelMethods: Pairs of human corneas procured for scientific purposes were used. The ACL were procured during femtosecond laser assisted cataract surgery and decellularized in water. Corneas were deswelled for 72h in our Active Storage Machine (ASM)(5). A central 4mm Descemetorhexis was performed. For each pair, one cornea received a 4mm ALC disc. The corneas were then placed back in the ASM with air tamponade for 72h. All corneas were then stored for 14 days in CorneaMax (Eurobio) and monitored by OCT. The endothelium was finally assessed using: 1/Hoechst 33342, Calcein‐AM and trypan blue staining for cell viability; 2/alizarin red staining for cell morphology; 3/immunostaining targeted CEC membrane proteins, mesenchymal transition markers and keratocytes.Results: Migration of CEC on the surface of the ALC was more extensive than on the bare stroma. Migrating cells were usually polynucleated and polygonal in both groups. Peripheral viable CECs (Calcein +) were comparable in both groups. Central corneal thicknesses were not statistically different.Conclusions: The presence of a ALC allows more extensive migration of CECs after 14 days in ASM compared with the DSO. The use of a decellularized ALC disc could therefore allow faster visual recovery for selected FECD patients eligible for DSO, particularly during combined cataract surgery.References
Borkar et al. Cornea. 2016 Oct; 35(10): 1267–73.
Iovieno et al. Can J Ophthalmol. 2022 Dec; 57(6): 402–7.
Huang et al. Cornea. 2018 Dec; 37(12): 1479–83.
Yoeruek et al. Cornea. 2009 May; 28(4): 416.
Garcin T et al. Am J Transplant. 2019 Jun; 19(6): 1641–51.
Genetically modified mesenchymal stem cells with CXCR4 and TSG‐6 as future cell therapy for the ocular surface: In vitro study of the cell migration and the regenerative capacity in an inflammation model
Authors: Figueroa‐Haro Jessica Nataly , de la Parte Esther González , Marceñido Beatriz , Vázquez Carmen García , de la Rosa Sara Galindo , Paniagua Marina López , Calonge Margarita , López‐Miguel Alberto , Miguel Teresa Nieto , de la Mata Sampedro Ana 
Published: January 2025

Aims/Purpose: Regeneration of the corneal epithelium, mediated by limbal epithelial stem cells, is essential for the maintenance of corneal transparency. Loss or dysfunction of these cells or their niche, known as limbal stem cell deficiency (LSCD), causes corneal inflammation, ulceration, neovascularization, chronic pain, and conjunctivalization, leading to corneal blindness. Mesenchymal stem cells (MSCs) are a safe and effective treatment for LSCD, however, there is controversy regarding their migration potential. The aim of this work is to enhance the migration and regenerative capacity of adipose tissue‐derived MSCs (AT‐MSCs) by overexpressing the TNF‐stimulated gene 6 (TSG‐6) and the chemokine receptor CXCR4, while maintaining their phenotype.Methods: AT‐MSCs were transduced with TSG‐6 and CXCR4 using lentiviral vectors. The immunophenotype of the transduced AT‐MSCs was analyzed evaluating the expression of CD14, CD19, CD34, CD45, HLA‐DR, CD73, CD90 and CD105. Moreover, the migration capacity and the regenerative potential of the modified AT‐MSCs were analyzed using a Transwell cell migration assay in the presence or absence of the pro‐inflammatory cytokine TNFα, and a wound healing assay in human corneal epithelial cells (HCE).Results: TSG‐6 and CXCR4‐modified AT‐MSCs expressed the MSCs surface markers, maintaining the immunophenotype. Both cells, CXCR4 or TSG‐6‐modified, showed significantly higher migration than control AT‐MSCs in standar conditions. Under inflammatory conditions, a significant increase in the migratory capacity of TSG‐6‐modified AT‐MSCs was observed compared to the control and the CXCR4‐modified ones. The HCE wound healing was faster in the presence of TSG‐6‐modified AT‐MSCs.Conclusions: TSG‐6 and CXCR4‐modified AT‐MSCs maintain the MSCs immunophenotype and improve their migration capacity under standar conditions. Transduction of AT‐MSCs with TSG‐6 enhances both migratory and regenerative capacity of AT‐MSCs under inflammatory conditions.
Quality control in corneal eye banking: Impact of preservation time on graft endothelium
Authors: Cabanas João Castro , Cardoso Daniel Ferreira , Martins Pedro Moreira , Soares Ricardo Machado , Ribeiro Ana Clara , Arêde Carlos , Sequeira Joaquim 
Published: January 2025

Aims/Purpose: To evaluate the impact of preservation duration on the endothelial quality of corneal grafts and to identify the most effective parameters for quality control of these grafts.Methods: Retrospective analysis of specular microscopy data from corneal grafts collected by the Cornea and Amniotic Membrane Department of Unidade Local de Saúde Gaia e Espinho between 2021 and 2024. According to department protocol, corneal grafts were stored at 4°C in Optisol‐GS (Bausch and Lomb, Rochester, USA) solution, and specular microscopy was performed at 24 hours (D0), day 5 (D5), and day 10 (D10) post‐harvest. Only grafts with at least two specular microscopy exams (D0‐D5) before transplantation were considered. Data collected included donor age, endothelial cell density (ECD), hexagonality (HEX), and coefficient of variation (VC) at all time points. Data was compared across all time points using repeated‐measures ANOVA adjusted for confounders, with a significance level set at 0.05.Results: Of 93 corneal grafts, 58 met the inclusion criteria, with 12 having specular microscopy analysis at D10. The mean donor age was 61.7 ± 12.9 years. Mean ECD was 2846 ± 434 cells/mm2 at D0, 3025 ± 535 cells/mm2 at D5, and 2880 ± 440 cells/mm2 at D10. Mean HEX was 58.7 ± 11.7% at D0, 51.1 ± 10.5% at D5, and 49.6 ± 12.3% at D10. Mean VC was 34.0 ± 6.7% at D0, 37.9 ± 6.2% at D5, and 38.5 ± 8.7% at D10. Variations in HEX and VC between D0 and D5 were statistically significant (p&lt; 0.001), while no significant difference was found between D5 and D10 (p = 0.915 and p = 0.274, respectively). These differences were independent of graft donor age (p > 0.05).Conclusions: In this study, preservation time affects the endothelial quality as represented by the decrease of cell HEX and increased VC, especially in the first days of preservation (D0‐D5) while this effect is more attenuated between D5 and D10. Moreover, these two parameters might be more reliable markers of endothelial cell quality in corneal grafts during preservation compared to ECD as this measure is more prone to exam variation as seen in our results.
Designing and testing anti‐scarring and anti‐inflammatory biomaterials for corneal implants: A promising alternative to human donors
Authors: Abu‐Dieh Anas , Om Boda , Thathapudi Neethi , Kiyaseh Mozhgan , Roudbaraki Mostafa , Robert Marie‐Claude , Hébert Mélanie , Jabbour Samir , Harissi‐Dagher Mona , Griffith May 
Published: January 2025

Purpose: Corneal blindness is mainly treated by cornea transplantation. However, there is a shortage of cornea donors for surgeries in many countries. Even with accessible donors, patients suffering from severe pathologies causing inflammation may not benefit as they are at high risk for graft rejection. The Griffith laboratory is the first to use acellular human collagen implants to regenerate high‐risk corneas in a group of patients. For broader clinical applications, scalable collagen‐like peptide (CLP) synthetic hydrogels are being developed. It is important to identify design patterns to ensure the implants do not cause inflammation.Methods: The growth of stromal fibroblasts cultured on CLP hydrogels with and without RGD groups are compared, with collagen gels and tissue culture plastic as controls. Cellular growth and viability on the different substrates were compared using the AmarBlue assay. Next, TGF‐β was added to the media to stimulate fibroblast differentiation into myofibroblasts. The latter has been linked to corneal scarring. The proportion of resulting myofibroblasts was determined by immunostaining using anti‐smooth muscle actin (SMA) antibody. Stromal cells seeded onto the hydrogels were also stained against fibronectin to study its implication due to RGD. Furthermore, the CLP‐based hydrogel was tested in vivo on alkali burnt BALB/c mice to investigate their practical biocompatibility and efficacy.Results: α‐SMA expression was observed in cells grown on CLP‐RGD containing hydrogels but not on tissue culture plastic or CLP‐only control. There was a positive fibronectin expression by cells cultured on CLP‐RGD hydrogels, on 5% collagen hydrogels and on the issue culture control. The CLP‐RGD hydrogel is a smooth and soft gel with desirable water content. The in vivo test showed that there was no sign of inflammation or angiogenesis in the cornea after three months, which can prove the great biocompatibility of the prepared CLP‐based hydrogel.Conclusions: This project allowed for the testing of cell growth on RGD‐containing CLP hydrogels, which has not been done before. Early results suggest that RGD groups within CLPs induced myofibroblast differentiation and potential pro‐inflammatory responses.
International standard pattern electroretinogram assessment of macular function is improved by additional large‐check responses
Authors: Georgiou Anne , Neveu Magella , Calcagni Antonio , Robson Anthony 
Published: January 2025

Aims/Purpose: The 2024 ISCEV Standard for pattern electroretinography (PERG) acknowledges the use of a non‐standard large check size as a potentially useful adjunct to Standard testing. This study aims to audit the additional use of responses to a large check size (focal ERGs; FERGs) in a heterogeneous group of patients.Methods: Recordings from successive patients tested at Moorfields Eye Hospital were retrospectively analyzed over 3 months. Best corrected visual acuity (VA) was recorded. A Standard checkerboard (0.75° checks; field size 13°x11°; 4.2 rps) was used to elicit PERGs and a coarse stimulus (check size 7.5°, field size 10°x10°, 4.4 rps) used to elicit FERGs for comparison. If the FERG (positive peak) was larger or of equal amplitude to P50, an optical contribution to PERG reduction was considered and remedial actions documented.Results: Data was obtained from 434 patients (864 eyes). Data from 18 eyes were excluded due to artefacts. In most cases (724/846 eyes, 86%) the PERG was larger than the FERG. The FERG was larger or equal to the P50 component in 14% of eyes (122/846) suggesting an optical contribution to P50 reduction (possible cause for optical degradation on referral in 51/122). In 10/122 autorefraction was performed before testing due to an improvement in VA with pinhole. In 13/122 autorefraction was prompted due to the FERG data, with 11 of these showing subsequent improvement in PERG P50 (4/11 of which normalized).Conclusions: The FERG helps to identify optical contributions to PERG P50 reduction, enabling adjustments that provide a more reliable and accurate assessment of macular function. The FERG is a useful adjunct to PERG testing, warranting consideration within future ISCEV Standard PERG protocols.Reference
Thompson, D.A., Bach, M., McAnany, J.J. et al. ISCEV Standard for clinical pattern electroretinography (2024 update). Doc Ophthalmol 148, 75‐85 (2024).