bluuebunny/crossref_metadata_2025_split huggingface dataset:
Visual acuity outcomes by causative mutation in the natural history of leber hereditary optic neuropathy: Analysis of historical data from Case Record Survey‐2 (CRS‐2)
Authors: Yu‐Wai‐Man Patrick , van Everdingen Judith , Leroy Bart , Krawczynski Maciej , Lamperti Costanza , Carelli Valerio , Llòria Xavier , Klopstock Thomas 
Published: January 2025

Aims/Purpose: The clinical progression of Leber hereditary optic neuropathy (LHON) is influenced by the causative mitochondrial DNA (mtDNA) mutation. The Case Record Survey‐2 (CRS‐2; NCT02796274) aimed to establish the natural history of LHON in idebenone‐naïve patients. Here, we report the 12‐ and 24‐month clinical outcomes by mutation.Methods: Data were extracted from case records (20 sites, 7 European countries) meeting the criteria: aged ≥12 y, m.11778G > A, m.3460G > A or m.14484T > C mtDNA mutation, onset of symptoms (OoS) after 1999, ≥2 visual acuity assessments (VAA) within 5y of OoS. Baseline (BL) was the first VAA after OoS; subacute/dynamic (S/D) and chronic eyes were ≤1 or > 1 y from OoS at BL, respectively. Spontaneous clinically relevant recovery, stabilisation and worsening (sCRR, sCRS and sCRW, respectively) were calculated as previously described.1 Eyes eligible for analysis had a VAA 12±3 or 24±3 months from BL.Results: Eligible eyes included 96 S/D and 11 chronic eyes for the 12‐month analysis and 44 S/D and 2 chronic eyes for the 24‐month analysis.At 12 months, rates of sCRR, sCRS and sCRW in overall S/D eyes were: 13% (12/96), 26% (11/42) and 66% (50/76), respectively. By mutation, these rates were: m.11778G > A: 9% (6/68), 23% (7/30), 70% (37/53); m.3460G > A: 0% (0/16), 29% (2/7), 82% (9/11); and m.14484T > C: 50% (6/12), 40% (2/5), 33% (4/12), respectively. There were few chronic eyes, with overall rates of 18% (2/11), 100% (2/2) and 67% (4/6), respectively.At 24 months, rates of sCRR, sCRS and sCRW in overall S/D eyes were: 27% (12/44), 46% (10/22) and 46% (16/35), respectively. By mutation, these rates were: m.11778G > A: 11% (3/27), 33% (5/15), 57% (13/23); m.3460G > A: 50% (7/14), 67% (4/6), 33% (3/9); and m.14484T > C: 67% (2/3), 100% (1/1), 0% (0/3), respectively.Conclusions: The CRS‐2 study offers important insights into the impact of causative mutation on the natural history of LHON.References
Yu‐Wai‐Man P et al. Cell Rep Med. 2024;5:101437.
Comparison of blind children's gait pre/post introduction of a wearable assistive safety device
Authors: Ambrose‐Zaken Grace , Bakshi Ishani , Chong Paul , Enzenauer Robert W. 
Published: January 2025

Aims/Purpose: Infants with congenital mobility visual impairment or blindness (MVI/B) walking delays are due to exposure and insufficient contact with their environment. Assistive safety devices provide contact and protection. [1,2] Our study measured foot motility/gait in pediatric patients with a MVI/B to quantify the benefits of wearing a Pediatric Belt Cane.Methods: Videos of fifty pediatric patients (Mean age = 26 mos, SD = 10.8) with a MVI/B Before and After were analyzed using the MediaPipe platform to perform gait analysis. Subsequent analyses included linear regression analysis and data smoothing to calculate metrics for foot mobility, approximate speed, step frequency, and estimated step lengths. T‐test analysis was performed to calculate the significance of differences in gait analyses.Results: Patients utilizing Pediatric Belt Canes showed significant percent increase in foot mobility (p < .05), percent improvement in approximate speed (p < .05), percent reduction in step frequency (p < .05), and percent increase in step length (p < .05).Conclusions: Pediatric Belt Canes lead to marked, quantifiable improvements in walking for children with a MVI/B, supporting the conclusion that assistive safety devices are a medical necessity in the care and management of all children with a MVI/B (e.g., lack visual preview). Further work increasing the choice of assistive devices is warranted for sport, blind children with motor impairments, etc.References: 1. Chong, P., Enzenauer, R., Ambrose‐Zaken, G. Comparative video gait analysis of assistance for cortically visually impaired Children. International Council of Ophthalmology, WOC, August 17, 2024, Vancouver. 2. Chong, P. Comparative video gait analysis of assistance for mobility visually impaired Children. AAPOS, April 8, 2024, Austin, TX.
Corneal epithelial thickness mapping precision in keratoconic eyes with two different optical coherence tomographers
Authors: Venkataraman Abinaya , Vandemoosdijk Stephanie , Samolov Branka , Dominguez‐Vicent Alberto 
Published: January 2025

Aims/Purpose: Corneal epithelial thickness measurement precision was evaluated with an anterior segment optical coherence tomography (AS‐OCT) and a posterior segment OCT adapted with an anterior module in subjects with keratoconus and healthy controls.Methods: The MS‐39 (spectral domain AS‐OCT) and the HS‐100 (posterior segment OCT with ASA‐1 adaptor) were used to measure the corneal epithelium. On each participant, three consecutive measurements were taken. The metrics used to describe the repeatability of each OCT were the within‐subject standard deviation (Sw) and repeatability limit (Rlim).Results: 81 controls (81 eyes) and 52 keratoconus subjects (80 eyes) were measured. The best repeatability was obtained in the central sector for both control and keratoconus groups with both MS‐39 and HS‐100. The Rlim never exceeded 5μm in any of the sectors for both groups with MS‐39. With the HS‐100, the Rlim never exceeded 7μm in any of the sectors for the control group and in all but one sector in the keratoconus group. In the keratoconus group, there was a weak negative correlation (p < 0.05) between the thinnest corneal thickness and their respective Sw for both instruments. For the control group, the correlations between the three different metrics (the thinnest epithelial thickness measured with the MS‐39, the thinnest corneal thickness measured with the MS‐39, and the thinnest corneal thickness measured with the Canon OCT) and their respective Sws were not statistically significant (p > 0.05).Conclusions: Both OCTs showed good repeatability to measure corneal epithelial thickness in both healthy and keratoconus eyes, independent on the history of corneal crosslinking or contact lens use.
Cosmetic keratopigmentation of anterior corneal stroma with modified micropuncture technique
Authors: Cyrino Laura Goldfarb , Garotti Giovanni , Vigga Paulo , Santo Ruth 
Published: January 2025

Aims/Purpose: Describe an innovative technique of ocular cosmetic conjunctival pigmentation and represent the cosmetic results, satisfaction, and improvement of the patients' quality of life and the safety indices of the anterior stromal keratopigmentation procedure with modified micropuncture technique.Methods: In this prospective cohort study with a single measurement at post‐intervention time, we perform superficial anterior keratopigmentation with stromal micropuncture in eyes with poor visual prognosis as an alternative method to contact lenses and ocular prostheses in fifty patients with leukomas at the Cornea Department of the University of São Paulo. Through an appropriate questionnaire, we will also evaluate the perception of the patients participating in this research on the effectiveness of tattooing in cosmetic improvement and social well‐being.Results: Among our 50 participants, 25 were men and 25 women. The average age was 53 (ranging from 7 to 85). 49 of them had no visual acuity with some degree of light perception, and the most common causes of leukoma were retinal detachment (34%) and glaucoma (32%). 37 participants reported high satisfaction with the procedure (74.0%; 95% CI = (60.4% ‐ 84.1%)), 45 participants reported increased social and professional well‐being (90.0%; 95%CI = (78.6% ‐ 95.7%)) and 100% of participants reported increased self‐esteem.Conclusions: The innovative technique of modified micropuncture for ocular cosmetic pigmentation of anterior corneal stromal proved to be safe, fast, and efficient, especially in economics as well in terms of cosmetics, and has the potential to impact the lives of patients and bring this alternative to this problem to countries and centers with limited resources and public health systems.References
Hasani H, Es’haghi A, Rafatnia S, Alilou S, Abolmaali M. Keratopigmentation: a comprehensive review. Eye (Lond). 2020 Jun;34(6):1039–46.
Stuve‐wiedemann syndrome and cornea consequences: A rare case report
Authors: Cyrino Laura Goldfarb , Miranda Bruna , Pina Luciana 
Published: January 2025

Aims/Purpose: Stuve‐Wiedemann Syndrome (STWS) is a rare genetic disorder inherited in an autosomal recessive manner. The condition leads to respiratory and feeding difficulties, as well as episodes of hyperthermia, typically resulting in death within the first two years of life. It is characterized by bone dysplasia, hypotonia, and dysautonomia, accompanied by ocular and neuropathic features. The absence of corneal reflexes, decreased blink reflexes, and corneal opacities are recognized markers. Here, we report a case of STWS with corneal hypoesthesia and opacity, highlighting the current challenges in management and treatment.Methods: A 16‐year‐old male was admitted to the Ophthalmology Department of the University of São Paulo in 2010 due to a history of multiple corneal ulcer episodes. At the slip lamp examination, he presented leukoma formation and corneal hypoesthesia. The patient also presented several orthopedic alterations. After a multidisciplinary investigation, the diagnosis of STWS was made, and follow‐up was conducted. He has been treated with lubricating eye drops and ointment for the last few years. Since 2014, he has not experienced corneal ulcers. At his last appointment in 2024, he kept corneal exposure due to decreased blink reflexes, leukomas in both eyes, mild superficial punctate keratitis and complained of dry eye and eye itching despite the treatment. Therefore, a tarsoconjunctival flap was indicated as a surgical method, having been employed due to persistent corneal involvement.Results: The case's challenges relate to the management and treatment of corneal involvement in patients with STWS, as most often, they are children who don’t express discomfort or show symptoms due to the characteristic neuropathy of their lesions. Additionally, it's essential to reduce corneal exposure and its consequences.Conclusions: Although rare, ophthalmologists must be aware of this ocular involvement in STWS for early diagnosis and appropriate management.References
Hernández‐García S et al. Neuroparalytic keratopathy in Stüve‐Wiedemann syndrome treated with tarsoconjunctival flap. Indian J Ophthalmol. 2023
Effect of postoperative subconjunctival corticosteroid injections in a multimodal approach for the treatment of severe symblepharon
Authors: Artemiev Dmitri 
Published: January 2025

Aims/Purpose: To report on the impact of additional subconjunctival corticosteroid injections in a subsequent multimodal treatment of a challenging case of symblepharon following a Roper Hall Grade III chemical burn.History and signs: A 42‐year‐old male patient was referred due to multiple failed treatment attempts for his corneal disease and severe symblepharon formation. The initial cause of the accident was a chemical burn on the right eye (OD) caused by potassium hydroxide. At the time of referral, extensive ocular surface damage was present with corneal vascularization, fibrovascular pannus, persistent central corneal ulcer, distichiasis, upper eyelid nasal entropion, and limbal stem cell deficiency (LSCD), with visual acuity reduced to finger counting.Results: To treat this patient's condition, we adopted a multimodal three‐step approach. The first step was to reconstruct the fornix, with additional preoperatively intensive topical therapy with autologous serum drops and antibiotic eye drops to reepithelialize the corneal ulcer. In the crucial postoperative period, we administered a subconjunctival injection of 0.5ml betamethasone and a week later 1ml triamcinolone to prevent recurrence of symblepharon. The healing process went well and there were no further signs of symblepharon recurrence three months later. To improve tissue modulation, we administered a subconjunctival injection of triamcinolone again to achieve a more lasting effect and planned step two, which included a limbal stem cell transplant and lastly a penetrating keratoplasty as the final step.Conclusions: There are numerous therapeutic approaches to treat symblepharon, which are primarily based on surgical procedures and these remain an important cornerstone for the chances of recovery. In addition to surgical treatment, postoperative adjustment is also crucial for success. With our new approach we took action in the fibrosis formation process by administering early postoperative subconjunctival injections, this to achieve better bioavailability.
Identification and quantification of CD3+ and HLA‐DR+ cells in pellets from low volume samples of human tears through an automated image‐based cell counter
Authors: Ciavarella Carmen , Versura Piera 
Published: January 2025

Aims/Purpose: Tears are a novel fluid source for biomarker analysis in several human diseases, becoming attractive for the rapid and less invasive collection method. The low sampling volume and the lack of standardized anlytical procedures are significant challenges. Here, we tested the performance of an automated image‐based cell counter for analysis and counting of CD3+ T lymphocytes and HLA‐DR+ cells in tear pellets.Methods: Tears aspirated from 10 healthy volunteers were centrifuged and pellets were fixed in 4% paraformaldehyde. Pellets were then resuspended in Bovine Serum Albumin (BSA) buffer and divided in two samples for parallel evaluation by Countess FL Automated Cell Counter and the flow cytometer Attune Cytpick (Thermo Fisher Scientific). Pellets were stained with Human Leukocyte Antigen‐ DR as marker of inflammation and CD3 as marker of T cells.Results: The total cell counting between flow cytometry and automated cell counter showed a significant correlation (R2 = 0.9587, p value = 0.0209). HLA‐DR and CD3 fluorescence percentages were comparable between the two methods, without significant differences (HLA‐DR positive cells: Countess 49%, Attune 48.6%; CD3 positive cells <5% in both estimations).Conclusions: The Automated Cell Counter is a promising approach to strengthen the application of tear fluids in the diagnosis of ocular surface diseases. The combination of cell counting with cell imaging into a bench instrument may overcome the limitations of flow cytometry due to the scant number of events in tear volumes. Further studies are aimed at optimizing the whole analytical workflow to bring the method in the daily practice.
Investigating dexpanthenol transfer to the anterior segment from coated contact lenses and aqueous solution
Authors: Santer Verena , El Guamra Adyl‐Michaёl , Kawaguchi Tohru , Kalia Yogeshvar N. , Lamrani Mouad 
Published: January 2025

Aims/Purpose: Dexpanthenol (Dxp) is a common excipient in topical formulations used in dermatology and ophthalmology. However, little is known about the absorption of Dxp into biological tissues. In this study we investigated the transfer of Dxp into the anterior segment – i.e. cornea and aqueous humor – first, from contact lenses (CL) following treatment with SOLOCARE AQUA® care solution and second, after administration of Bepanthen® and Siccaprotect® eye drops. All products contained approximately equivalent amounts of Dxp (2–3%).Methods: A bioanalytical method for the quantification of Dxp by UHPLC MS/MS was validated. The initial experiments evaluated the ad/absorption of Dxp from the SOLOCARE AQUA® care solution onto FDA class representative CL. Then, ex vivo porcine eye globes were mounted in an eye globe holder developed inhouse, with simulated tear flow, and Dxp uptake into the anterior segment from SOLOCARE AQUA® treated CL and eye drops was investigated.Results: Dxp ad/absorption in CL was correlated to exposure time and CL material. Following exposure to Dxp‐soaked CL and eye drops, transport of Dxp through porcine cornea to the aqueous humor was found in all experimental conditions. However, there was a statistically significant difference in the concentrations measured after CL application and eye drop instillation. Direct application of Dxp containing eye drops resulted in higher Dxp deposition in the anterior segment than the SOLOCARE AQUA® treated CL.Conclusions: In this benchmark study we investigated the deposition of Dxp in the anterior segment of excised porcine eyes from CL treated with a care solution and commercially available eye drops. Despite the excipient Dxp being classified as Generally Recognized as Safe (GRAS), the inferior absorption of the substance from SOLOCARE AQUA® washed CL compared to approved Dxp containing eye drops is considered preferable with regard to medical device safety.
Marginal keratitis after intravitreal injection of bevacizumab
Authors: Aroco Clara Lara , de los Ángeles Ibáñez Ruiz María , Martín Silvia Beatriz De Miguel , Escribano Rosa María Jiménez 
Published: January 2025

Aims/Purpose: To report a case of marginal keratitis that developed after intravitreal bevacizumab (Avastin) injection.Methods: A 88‐year‐old woman with Age‐related macular degeneration (AMD) and macular edema in both eyes received four intravitreal injection of bevacizumab (Avastin) in left eye and five in right eye. No previous history of herpes.Results: Two days following the fifth injection of Avastin in the patient's right eye, she experienced sensations akin to having a foreign body, accompanied by redness and a decrease in visual acuity in that eye. Examination with a slit lamp revealed peripheral infiltrates beneath the corneal epithelium, delineated from the limbus by a clear zone. Additionally, there was corneal edema with folds in the endothelium and a mild anterior chamber reaction. No presence of hypopyon was noted. The patient's symptoms showed favorable response to topical steroid and topic and oral antibiotic medicationsConclusions: The intravitreal administration of bevacizumab carries a risk of inducing hypersensitivity reactions like marginal keratitis. To our knowledge, this is the first documented account of marginal keratitis after intravitreal bevacizumab injection.References
Farrell DA, Deacon S, Mauger T. "Marginal keratitis following COVID 19 vaccination". IDCases. 2022 Jun 15; 29: e01536. doi: 10.1016/j.idcr.2022.e01536. PMID: 35756698; PMCID: PMC9212909
Aslan Bayhan S, Bayhan HA, Adam M, Gürdal C. Marginal keratitis after intravitreal injection of ranibizumab. Cornea. 2014 Nov; 33(11): 1238‐9. doi: 10.1097/ICO.0000000000000255. PMID: 25222003
Anti‐pseudomonal effect of nephrite‐impregnated contact lenses
Authors: Lee Jieun , Kim Sangyoon 
Published: January 2025

Aims/Purpose: This study investigates the efficacy of nephrite‐impregnated contact lenses (NICLs) against Pseudomonas aeruginosa.Methods: After inoculating the lenses with a standardized Pseudomonas aeruginosa strain, three types of contact lenses were assessed: nephrite‐impregnated, conventional, and cosmetic. We performed a quantitative assessment of bacterial adhesion using viable cell count techniques. The lens surface characterization involved atomic force microscopy (AFM) and scanning electron microscopy (SEM) for detailed topographical analysis and bacterial attachment patterns. The safety evaluation in rabbits examined parameters such as corneal clarity, thickness, and endothelial cell count over time, providing a thorough assessment of biocompatibility and safety.Results: Both conventional and cosmetic CLs (n = 258 ± 2.9 × 104, 368 ± 2.2 × 104) showed significantly decreased number of attached bacteria when compared with those without nephrite impregnation (n = 134 ± 0.8 × 104, 238 ± 2.5 × 104, p < 0.0001, respectively). AFM and SEM revealed that P. aeruginosa was less attached to the nephrite‐impregnated CLs than to the conventional and cosmetic CLs, although those with nephrite impregnation had rougher surface. In the safety test, there were no significant differences in the findings between four groups, and the clarity and stability of all corneas were preserved.Conclusions: Nephrite, used in traditional medicine, is shown to reduce Pseudomonas aeruginosa adhesion on CLs, potentially preventing infections. Employing the Flusier method, the study embeds nephrite in CLs, reducing bacterial attachment despite a rougher surface. Safety evaluations in rabbits reveal no significant complications, suggesting its safety. The study, however, has limitations like the short testing duration and unclear anti‐pseudomonal mechanisms. Further research is needed to validate nephrite‐impregnated CLs for human use, but this study lays a promising groundwork for developing safe, anti‐microbial CLs.
Comparison of mice from two different vendors for dry eye disease mouse model
Authors: Thapa Rubina , Lappeteläinen Birgitta , Kolehmainen Anni , Koponen Anna Mari , Partanen Päivi , Lappalainen Eerik , Härkönen Kirsti , Pakarinen Oona , Varis Sanni , Haapaniemi Anne Mari , Pietikäinen Piia , Vähätupa Maria 
Published: January 2025

Aims/Purpose: The purpose of the study was to compare corneal surface damage at baseline and 20 days after induction of dry eye disease (DED) in mice from two different vendors: Janvier Labs, France, and The Jackson Laboratory, USA.Methods: 120 C57BL/6JRj female mice (Janvier Labs, Saint‐Berthevin, France) and 120 C57BL/6J female mice (The Jackson Laboratory, Bar Harbor, ME USA) were received at our facility and corneal fluorescein staining (CFS) was performed to evaluate corneal surface damage at baseline. 40 mice with CFS score ranging from 0‐2 were selected for DED study. DED was induced in 8‐week‐old mice by administering scopolamine (500 μg/mouse/dose) subcutaneously three times per day for 20 days. Mice were housed in the dry eye inducing chamber (DEIC, 12l/min airflow and 13 % humidity on average). Mice were treated topically with Ikervis® or phosphate‐buffered saline (PBS) twice daily (5 μl/eye). Corneal surface damage was assessed using CFS on day 13 and day 20, and with rose bengal staining (RBS) on day 21.Results: The baseline CFS score (median of 2) did not differ in mice from Janvier and Jackson. DED was successfully induced in mice from both vendors. However, Janvier mice developed more severe corneal damage on day 13 (median score 3 vs 2, respectively; p < 0.05). CFS score in Jackson mice did not reach statistical difference on day 20 as compared to baseline (median score 1 vs 2, respectively; p = 0.21). Mice treated with Ikervis® did not differ from PBS‐treated mice in corneal surface damage as assessed using CFS on Day 13 and 20 and RBS on Day 21. RBS staining results from PBS‐treated mice were similar in Janvier and Jackson mice.Conclusions: The corneal damage at the baseline was similar in both vendors’ mice. The successful induction of dry eye disease was evident in both vendors’ mice based on day 13 CFS data. However, the phenotype persisted only with Janvier mice. This dosing regimen of Ikervis® failed to show any therapeutic effect as assessed from CFS and RBS scoring in mice from either of the vendors.