bluuebunny/crossref_metadata_2025_split huggingface dataset:
Para‐phenylenediamine hair dye and dry eye symptoms: A cross‐sectional study
Authors: Jugnarain Davina , Birss Matthew , Mohamudally Raawiyah , Chaabane‐Rajah Nedjema , Carrim Zia 
Published: January 2024

Aims/Purpose: Para‐phenylenediamine is a common constituent in black hair dye which is well‐associated with irritant dermatitis. Ocular complications include blepharoconjunctivitis, dry eye disease and allergic eye disease (1), mostly reported in case studies. We conducted a cross‐sectional study to establish the prevalence of dry eye symptoms in black hair dye users, and its association with irritant dermatitis, sleeping position and frequency of hair dye use.Methods: This cross‐sectional study was conducted online among Facebook followers of an ophthalmology clinic based in Mauritius. 100 responses were gathered between November 2020 and May 2022. Participants included in the study were all users of black hair dye, over the age of 18 and of either sex. Patients with potential confounding causes of dry eye disease symptoms were not excluded from the study, but a separate analysis was conducted excluding them. Data was subsequently analysed using R statistical software.Results: Most participants were female (88%) and excluding those with confounding causes of dry eye disease, 57% of participants reported ocular symptoms, such as grittiness, blurry vision and red eyes. 34% of these patients also reported scalp dermatitis. Prevalence of ocular symptoms increased with duration of hair dye use. However, no association was found between either rates of irritant scalp dermatitis, sleeping position or frequency of hair dye use and ocular symptoms.Conclusions: We have found a high prevalence of dry eye symptoms among black hair dye users, compared to the prevalence previously described in the literature (28.2% by Golińska‐Zach et al.) (1), with a prolonged duration of hair dye use being a risk factor. Larger scale studies are needed to characterize the influence of para‐phenylenediamine hair dye on ocular surface disease, including assessment of tear film properties and meibomian gland dysfunction.Reference1. Golińska‐Zach A, Krawczyk‐Szulc P, Wiszniewska M, Nowakowska‐Świrta E, Świerczyńska‐Machura D, Tymoszuk D, et al. Sensitization to occupational allergens in hairdressing apprentices diagnosed already before entering vocational training. Med Pr [Internet]. 2016 [cited 2022 Apr 25]; 67(5): 567–75. Available from: https://pubmed.ncbi.nlm.nih.gov/27819696/
Smoking, diabetes mellitus and obesity as risk factors for the degree of fuchs endothelial corneal dystrophy (FECD)
Authors: Zwingelberg Sarah 
Published: January 2024

Aims/Purpose: To detect environmental factors, which may be possible risk factors in the disease course of Fuchs endothelial corneal dystrophy (FECD).Methods: Evaluation of patients with FECD registered in the FECD genetics database of the Center for Ophthalmology, University Hospital Cologne, from 2018 to 2019. For the evaluation, disease onset, central corneal thickness (CCT), best corrected visual acuity (BSCVA, logMAR), and age‐related Krachmer grading were correlated with the presence of diabetes mellitus (DM), body mass index (BMI), and smoking behaviour. Depending on the variables studied, differences between groups were examined by Mann–Whitney U test and chi‐square test. The significance level was 5%. Krachmer Grading was age‐corrected by using ordinal regression in the mediation analysis. For the mediation analysis the Kenny and Barron 4 Step Analysis was used.Results: 403 patients with FECD were included in the analysis. The mean age at diagnosis was 63.1 (±13.2) years. The female‐to‐male ratio was 1.46:1. Patients with a BMI of 30.0–34.9 kg/m2 developed FECD significantly earlier than patients with a BMI < 30 kg/m2 (p = 0.001). Patients with DM showed significantly more often an age corrected Krachmer grade of 5 compared to patients without DM (p = 0.015). Using the mediation analysis, the presence of DM correlated with age‐corrected Krachmer Grade 5 (p = 0.015), and the presence of DM correlated with BMI of 30.0–34.9 kg/m2 (p = 0.012). BMI of 30.0–34.9 kg/m2 exerts a significant effect on age‐corrected Krachmer grading grade 5 with p = 0.005. The effect of DM on age‐corrected Krachmer Grading 5 is significantly mediated by BMI‐ Group 4 using Kenny and Barron 4 Step Analysis, p = 0.013.Conclusions: Our study shows for the first time that obese individuals develop FECD significantly earlier than non‐obese individuals. Oestrogen secretion in premenopausal women occurs mainly in the ovaries, whereas postmenopausal oestrogens are produced in adipose tissue. Together with gender as a risk factor, this may indicate that oestrogens have a relevant influence on disease progression. Initial laboratory work has shown that oestrogen metabolites have genotoxic and apoptotic effects on corneal endothelial cells.
The role of exocytotic proteins in the (dys)regulation of human reflex tearing and aqueous‐deficient dry eye syndrome
Authors: Francis Alfred Francis Pakkam John , Manicam Caroline , Neumann Fabian , Pfeiffer Norbert , Grus Franz , Perumal Natarajan 
Published: January 2024

Aims/Purpose: Reflex tears triggered by various external and internal stimuli play vital functions in the protection of the ocular surface and visual acuity. The impairment of the molecular processes involved in reflex tearing is conjectured to be associated with the progression of dry eye syndrome (DES). Therefore, this study was undertaken to unravel the intricate proteome changes in the reflex and DES tears.Methods: Thirty six subjects underwent basic secretory test (BST) via Schirmer I (without anaesthetics) to determine the secretory rate of the lacrimal gland due to the irritating nature of the strip and were divided into reflex (RF, n = 12, BST = 35.0 ± 0.0), normal (NR, n = 12, BST = 15.3 ± 3.0) and severe aqueous‐deficient DES (DRY, n = 12, BST = 3.4 ± 1.4). The individual tear samples were analysed employing the state‐of‐the‐art mass spectrometry‐based proteomics strategy, followed by bioinformatics analyses to elucidate the underlying molecular processes.Results: A total of 293 and 237 proteins were found to be significantly (p < 0.05) differentially regulated in the RFL vs. NR (up‐regulated, UR = 12; down‐regulated, DR = 281) and DRY vs. NR (UR = 197; DR = 40), respectively. The hallmark of this study was the identification of 10 lacrimal gland‐specific proteins (e.g., LYZ, LCN1, LTF, PRR4, ZG16B) secreted mainly via the exocytotic pathway, which were significantly up‐regulated in the RFL vs. NR but down‐regulated in the DRY vs. NR. Antibacterial response was also significantly activated in RFL (p = 1.9 × 10−2) compared to DRY (p > 0.05). The activated inflammatory response (e.g. S100A8/A9, ANXA1) associated with DRY (p = 2.7 × 10−8, z = 4.0) was found to be inhibited in the RFL (p = 2.7 × 10−9, z = −3.5). Likewise, proteins involved in glycolysis (z = −2.8), acute phase response (z = −2.7) and actin cytoskeleton signalling (z = −2.1) were also inhibited in the RFL compared to DRY.Conclusions: In summary, this study has demonstrated that protein markers involved in the exocytotic pathway play major roles in the production of reflex tears and their regulation is impaired in the DES. Importantly, the abrogation of the vicious cycle of pathways involved in the progression of DES, especially inflammation, was observed in the reflex tears, which may be the key for the protection and maintenance of dynamic balance of the ocular surface.
In‐depth study of the mucoadhesive and lubricating properties of Hyalistil SYNFO and other sodium hyaluronate‐based eye drops
Authors: Abbate Ilenia , Pricoco Angelo , Spina Donato , De Pasquale Giuseppe , Zappulla Cristina , Curatolo Maria Cristina , Viola Santa 
Published: January 2024

Purpose: Several sodium hyaluronate (SH) eye drops formulations are widely used for the management of dry eye disease (DED). Hyalistil SYNFO is an eye drops based on SH and xanthan gum and osmoprotectants (glycine and betaine). The aim of our study was to evaluate viscosity and mucoadhesion profiles of Hyalistil SYNFO with respect to other SH‐based eye drops, and to investigate their ability to protect the corneal surface from dehydration.Methods: The physicochemical properties, in term of viscoelastic and mucoadhesive behaviour, were evaluated by means of a rheometer, TA‐XT2 texture analyzer and zeta potential determination. An in vitro dehydration model was used to demonstrate the lubricant effect of Hyalistil SYNFO compared to other commercially available SH‐based eye drops on human corneal epithelial cells (HCE).Results: The rheological profiles indicated that Hyalistil SYNFO exhibits a viscoelastic behaviour under shear strain showing a characteristic curve owing to its specific molecular properties. Evaluations of detachment force of tested formulations resulting in a strengthening of the mucin‐formulation interface showed that Hyalistil SYNFO exhibited a stronger and significant mucoadhesion calculated as percentage compared to mucin and other SH‐based products. The occurring interaction between formulation and mucin was also demonstrated by the variations in zeta potential measured by the mucin‐eye drops mixture compared to mucin or product alone. The in vitro study on HCE cells demonstrated that Hyalistil SYNFO, compared to others formulation, was able to protect corneal epithelial cells from dehydration.Conclusions: The pseudoplastic profile and increased mucoadhesive strength, due to the presence of both SH and xanthan gum, may lead to an improved residence time of Hyalistil SYNFO on the corneal epithelium ensuring relief during the treatment of DED. Moreover, the effect against dehydration improves eye lubrication and corneal cell protection.
Mask‐associated dry eye syndrome according to sex
Authors: Larraz Marta Sancho , Blasco‐Martinez Alejandro 
Published: January 2024

Aims/Purpose: The aim of this study was to evaluate the impact of the mask on the ocular symptoms of dry eye, Mask‐Associated Dry Eye Syndrome (MADE syndrome); according to sex.Methods: The population was divided into two groups: wearers, and non‐wearers of masks. Then, these groups were divided by sex. The group without mask was obtained from a database of control subjects. The group of subjects with a mask were people who use it for at least 3 h in a row every day. Subjects with pathologies with ophthalmological repercussion or previous surgeries were excluded. Subjective questionnaires were performed: OSDI, SANDE and CLEDQ‐8 tests adapted to the use of a mask. Psychological symptoms were also studied with the Brief Symptom Inventory (BSI). In addition, objective clinical signs were evaluated with Keratograph 5 M®, taking measurements of tear meniscus height, NIBUT and ocular redness.Results: Subjects without masks showed statistically significant differences between men and women in the values of ocular redness (p‐value < 0.01); and in the rates of depression and interpersonal sensitivity (p‐value < 0.01). The group of subjects with a mask show significant differences between men and women in the values of CLEDQ‐8 and OSDI (p‐value < 0.05) and SANDE (p‐value < 0.01). Differences were also observed in tear meniscus height (p‐value < 0.05) and ocular redness (p‐value < 0.01); and in somatization and interpersonal sensitivity (p‐value < 0.05); obsession‐compulsion, depression and psychoticism (p‐value < 0.01).Conclusions: The group of women with mask obtained an increase in the symptomatic tests compared to the group of men. The group of men showed higher values of ocular redness in mask carriers; but without the mask, the group of women showed the greatest redness. Finally, it was also observed that the group of women had an increase in BSI rates with and without wearing a mask; the first case being the most pronounced.
Is it really keratoconus ‐ topographic mimicry
Authors: Wykrota Agata , Seitz Berthold , Flockerzi Elias 
Published: January 2024

Aims/Purpose: The aim of this case series is to present eyes with topographic keratoconus configuration, but in which objectifiable no keratoconus exists and thus a so‐called pseudo‐keratoconus is present.Methods: Inclusion criteria were a topographic classification of the cornea as keratoconus by Scheimpflug imaging using the topographic keratoconus classification TKC and a typical elevation data profile with irregular astigmatism and slope (= Ansteilung) of the cornea. Clinical image by slit lamp examination, best‐corrected visual acuity and Scheimpflug tomography of the anterior segment of the eye (Pentacam®, OCULUS, Wetzlar, Germany) were analysed.Results: In our case series, 33 eyes of 23 patients were included. The mean age was 51 (±16) years and the ratio of females to males was balanced. The mean Kmax was 51.1 (±7.1) dioptres. The mean corneal thickness at the thinnest point was 517 (±80) μm. The best‐corrected decimal visual acuity was 0.47 (±0.27). The study eyes were divided into 3 groups according to the underlying cause of the topographic changes. One group included corneal diseases with inferior slope in topography (corneal scar n = 9, Map‐Dot‐Fingerprint dystrophy n = 6, Fuchs endothelial dystrophy n = 5, vortex keratopathy n = 2). The second group had a superior corneal slope that could be interpreted as a superior keratoconus configuration (Map‐Dot‐Fingerprint dystrophy n = 5, irregular astigmatism without other corneal pathology n = 2, Salzmann corneal degeneration n = 1, corneal scar n = 1). The third group included eyes with postoperative newly occurring keratoconus configuration after phototherapeutic keratectomy (n = 2).Conclusions: This case series shows that different corneal pathologies can imitate a topographic keratoconus configuration. The identification – not least at the slit lamp – and differentiation of these pathologies from keratoconus are important in daily practice with regard to counselling of the patients and further treatment.
Clinical phase 1 safety and tolerability evaluation of sustained release silica composite eye drops in human subjects
Authors: Kaarniranta Kai , Reay Marcus , Leino Lasse , Kievari Sari , Hartikainen Arto , Martikainen Oona , Kemiläinen Benjam 
Published: January 2024

Aims/Purpose: Most ocular disease is managed at least in part by use of eye drops. Many of these eye drops require multiple doses per day, as well as good patient compliance to relieve patients from incapacitating symptoms. To address this treatment burden, a Silica Matrix long‐acting eye drop technology was developed to offer a once‐a‐day (QD) dosing schedule. The aim of this study was to evaluate safety and tolerability of QD repeated dosing of silica composite eye drop platform in healthy volunteers for 15 days.Methods: 24 healthy volunteers were recruited to a randomized, double blinded, placebo‐controlled phase 1 clinical trial for repeated, QD dosing of silica composite eye drops over 15 days. Half of the subjects received a demulcent containing silica composite eye drops and the other half received plain silica composite eye drops (i.e., placebo). A single drop was applied QD in the cul‐de‐sac of one eye, and safety and tolerability was assessed by a blinded Investigator, including examination of outer eye structures and anterior chamber as well as interblink interval and tear fluid break‐up time (t0, 6h, D2, D3, D7, D11 and D15), lens examination (microscopic), change in visual acuity (EDTRS) and intra‐ocular pressure (t0 and D15). Ocular discomfort was assessed by volunteer questionnaire at t0, 6h, D3, D7, D11 and D15.Results: At submission, 13 subjects have completed the study and 11 are still under investigation. No significant differences in tolerability were observed between treated and untreated eyes, with no relevant adverse events. Volunteer questionnaire results indicate that 71% regarded instillation discomfort as mild, 22% moderate and 7% had no symptoms. Discomfort lasted less than 1‐min in 99% of responses.Conclusions: The results indicate that silica composite eye drops are safe and well tolerated in healthy volunteers when applied QD. This forms a good basis for development of sustained release topical ocular products for delivery of pharmacologically active agents in eye diseases.
Development of a novel multi‐stimulus ocular surface aesthesiometer system
Authors: Murphy Paul , Mungalsingh Melanie , Peterson Sean , Thompson Ben 
Published: January 2024

Aims/Purpose: To report the development of a novel, air‐based, aesthesiometer capable of producing and applying multiple stimuli of differing intensity, separated by time and/or ocular surface location.Methods: Individual micro‐blowers (Murata Manufacturing Co., Japan) were combined with an exit airflow nozzle into an integrated stimulus unit (ISU) that produced a controlled exit airflow through the nozzle exit. Stimulus intensity, duration, and repetition, as a feature of airflow, was managed for each ISU using a designed software. The software also controlled stimulus sequencing for multiple ISU in series. Stimulus airflow consistency and characteristics were assessed using two nozzle diameters (0.5 and 1.6 mm) for: (i) airflow pattern/trajectory; (ii) airflow surface dispersion; (iii) force of airflow; (iv) thermal effects; (v) time delay and spatial separation.Results: Stimulus characteristics: (i) airflow is coherent at proposed test distance (1 cm) and spread rate is constant irrespective of stimulus strength, airflow diameter at 1 cm: 1.8–2.1 mm; (ii) airflow disperses over surface and dispersion increases with increasing airflow rate; (iii) consistent, small force (10−4 N) is produced and varies with airflow rate; (iv) size of thermal effects depends on airflow rate; (v) single stimuli, repeat single stimuli with variable time‐delay, simultaneous multiple stimuli or with inter‐stimulus time delay can be produced.Conclusions: The novel ISU can produce repeatable, consistent air pulses (stimuli) under software control. Nozzle diameter has an influence on airflow coherence/dispersion. Single or multiple simultaneous stimuli with/without time delays, of differing intensity and duration, can be delivered to ocular surface. Multiple ISU allows presentation of multiple simultaneous stimuli that may provide an alternative method for assessing ocular surface sensitivity, and facilitate investigation of signal processing involved in ocular surface nerve summation.
Association between self‐reported eye health and self‐reported general health. Results from the FOREVER questionnaire
Authors: Andreasen Jens Rovelt , Freiberg Josefine , Kolko Miriam 
Published: January 2024

Aims/Purpose: This study aimed to investigate the association between self‐reported eye health and general health using questionnaire data collected in the Project FOREVER (Finding Ophthalmic Risk and Evaluating the Value of Eye exams and their predictive Reliability).Methods: A subset of questionnaire responses collected in Project FOREVER from June 2022 to May 11th, 2023, was analysed. Respondents rated their eye health and general on scales from 1 (excellent) to 5 (poor). Spearman's Rank Test and ordinal logistic regression models were employed to assess the correlation and association.Results: The analysis included 42 568 respondents with a mean age of 55.0 (15.0) years, of whom 62.6% were women. Among them, 10% reported having an eye disease, with cataract, glaucoma, and age‐related macular degeneration being the most commonly reported eye diseases. The Spearman's rank test revealed a significant and moderate positive correlation (rho = 0.24) between self‐reported eye health and general health. Moreover, general health showed significant effects across its different levels, with higher ratings associated with an increased likelihood of being in a higher category of eye health. All p‐values for the associations were below 0.05.Conclusions: Our findings indicate a strong association between self‐reported eye health and general health. Higher ratings of general health were linked to an increased likelihood of being in a higher category of eye health, underscoring the importance of considering both aspects in overall health assessments.
Molecular characterization of metastatic progression in patient derived xenograft models of malignant uveal melanoma
Authors: Demková Lucia , Furdova Alena , Kajabová Viera Horváthová , Babál Pavel , Smolkova Bozena , Šoltýsová Andrea 
Published: January 2024

Aims/Purpose: It has been observed that large UM lesions with significant infiltration of macrophages and CD8+ T cells exhibit specific genetic profiles that increase the risk of liver metastasis. Additionally, recent discoveries of DNA methylation changes in Class 2 tumours undergoing metastasis suggest a potential role of epigenetic alterations in UM progression.Methods: To identify factors involved in UM metastasis, we implanted 25 viable UM tumours (consisting of 11 Class 1 tumours with a good prognosis and 14 Class 2 tumours with a poor prognosis) subcutaneously into immunodeficient NSG mice. From these, we successfully established ten patient‐derived xenografts (PDXs) using Class 2 tumour tissues. Two metastatic PDXs were derived from liver (UM50) and peritoneal (UM58) metastases spontaneously developed on mice.Results: Comprehensive characterization of both primary tumours and PDX tissues was performed using bulk transcriptomics and methylomics techniques. Among the enriched metabolic pathways identified in the liver metastasis‐derived PDX tissue of sample UM50 compared to the PDX tissue from the primary tumour, four were related to epigenetic regulation, including the activation of rRNA expression by ERCC6 and EHMT2, methylation of histones and DNA by Polycomb Repressive Complex 2 (PRC2), regulation of rRNA expression by NAD‐dependent Deacetylase Sirtuin‐1, and the DNA methylation pathway.Conclusions: These findings highlight the potential importance of epigenetic deregulation in UM progression and provide a foundation for future investigations. Further analysis using the Chromium Single Cell ATAC platform to examine chromatin accessibility at the single‐cell level in primary and metastatic PDX tissues of UM50 and UM58 that are ongoing can contribute to unravelling the precise role of epigenetic alterations in UM metastasis. Continued research in this area may lead to the development of novel therapeutic strategies targeting epigenetic mechanisms and improving outcomes for patients with metastatic UM.