bluuebunny/crossref_metadata_2025 huggingface dataset:
Secretory autophagy markers are upregulated in age‐related macular degeneration
Authors: Gurubaran Iswariyaraja Sridevi , Koskela Ali , Kaarniranta Kai
Published: January 2025

Aims/Purpose: Our previous studies have shown an increasing correlation between dysfunctional autophagy and the progression of age‐related macular degeneration (AMD). In this study, we investigated secretory autophagy, an unconventional process involving the secretion of cytosolic leaderless cargos (proteins without N‐terminal peptides) into the extracellular space. We analyzed the signaling pathways involving secretory autophagy in retinal pigment epithelial cells.

Methods: Enucleated eyes from age‐matched controls (n = 9), dry (n = 6), and wet (n = 4) AMD donors were fixed and embedded in paraffin. From paraffin blocks, 5 μm‐thick parasagittal serial sections were cut, immunostained, and analyzed using the color deconvolution method in ImageJ. Clinical sample validation was based on patient registry history and optical coherent tomography (OCT) images.

Results: Our data revealed a significant increase in the selective autophagy marker sequestosome 1/p62 (p ≤ 0.0179) in AMD samples. Similarly, secretory autophagy markers Tripartite Motif Containing 16 (TRIM16) (p ≤ 0.0001), vesicle‐trafficking protein Sec22B (p ≤ 0.0001), ferritin (p ≤ 0.0001), cytokine IL1‐β (p ≤ 0.0001), and Galectin‐8 (p ≤ 0.0001) exhibited increased staining levels in AMD samples.

Conclusions: Secretory autophagy markers are upregulated in the retinal pigment epithelial cells (RPE) of clinically diagnosed cadaver AMD samples. We believe that secretory autophagy may open novel therapy strategies for AMD.
Inflammation and microglia activation contribute to retinal degeneration in peripherin‐2 mutant mice model
Authors: Cuenca Nicolas , Vidal‐Gil Lorena , Missonier Enola , Castillo Carla Sánchez , Kutsyr Oksana , Fernández‐Sánchez Laura , Albertos‐Arranz Henar , Sahin Ceren , Pastor‐Mas Marina , Saez Xavier Sanchez , Maneu Victoria , LAX Pedro , Martínez‐Gil Natalia
Published: January 2025

Purpose: Central Areolar Choroidal Dystrophy (CACD) is a monogenic hereditary retinal disorder characterized by progressive retinal degeneration. In most cases, CACD presents an autosomal dominant inheritance pattern in which patients carry a single mutation in the peripherin (PRPRH2) gene. This study presents a functional, immunohistochemical and transcriptomic analysis of the retinas of a mouse model carrying the p.Arg195Leu mutation in the PRPH2 gene.

Methods: Neural retinas from Prph2WT/WT and Prph2WT/KI mice were used at different ages. Electroretinogram (ERG) was used to evaluate the retinal response. Immunostaining against CD68 and Iba1 was performed in retinal sections to characterize the activation of inflammatory retinal cells. Also, TO‐PRO staining was used to study ONL retinal thickness. The expression profile of mRNAs across the progression of the retinal degeneration, was analyzed by RNA‐Seq. R software and DESeq2 package together with pathway enrichment were used to perform the analysis.

Results: ERG responses showed a decrease in a and b‐wave values in Prph2 WT/KI compared to Prph2 WT/WT at late stages of the disease. Also, the retinal thickness decreased in an age‐dependent manner. Compared to control, RNA‐seq analysis identified more than 2,000 differential expression genes in Prph2WT/KI mice. An upregulation of anti‐inflammatory genes was found young mice, in contrast with the proinflammatory profile observed in older ones. These changes were also confirmed by CD68 and Iba1 increased immunoreactivity.

Conclusions: The retinas of young Prph2WT/KI mice showed an anti‐inflammatory profile without any impact on retinal thickness or function, compared to control mice. However, at late stages of the disease, the loss of visual function and retinal thickness is accompanied by an activation of pro‐inflammatory response. Thus, the modulation of immune system response could be crucial in managing the progression of the disease.
Correlation between systemic hypertension and glaucoma risk: Insights from a population‐based glaucoma screening (NCT 05875090)
Authors: Monteiro Bernardo , Lima‐Cabrita Afonso , Whitfield Rafael , Lobo Vasco , Marques Rodrigo , Ourique Matilde , Varandas Teresa , Barão Rafael , Pazos Marta , Stalmans Ingeborg , Abegão‐Pinto Luís
Published: January 2025

Aims/Purpose: To evaluate the association between glaucoma referral and systemic hypertension (SH) in participants in a population‐based glaucoma screening using artificial intelligence (AI).

Methods: compare the odds of glaucoma referral between participants with and without SH. Glaucoma referral was defined by intraocular pressure (IOP) ≥ 24mmHg or AI index ≥ 0.73. Clinical data was extracted from electronical medical records. Statistical analyses included descriptive and bivariate statistics.

Results: Data from 837 participants were analyzed, comprising 54% males, with an average age of 62±4 years, across 11 functional units of Santa Maria Local Health Unit. 63,4% (n = 530) of this cohort had SH, of which 81.1% were on angiotensin‐converting enzyme (ACE) inhibitors. SH was not a risk factor for positive Glaucoma referral (SH = 8.5% vs non‐SH = 6,86%; OR 1.663; 95% CI 0.827‐3.345). Interestingly, there appears to be a potential association between SH and a higher IOP (p = 0.024). Furthermore, there also appears to be a higher AI mean between hypertensive patients who are medicated with ACE inhibitors and those who are not (0.58 vs 0.52, p = 0.003).

Conclusions: Our findings suggest a potential association between SH and a higher IOP but not with the AI index. Type of anti‐SH medication may influence optic disc damage assessment and thus may need to be considered in the management of glaucoma patients.
Comparison between measurements of the circumpapillary nerve fiber layer thickness and the thickness of the waist of the nerve fiber layer in the optic nerve head
Authors: Holm Jonatan , Kisonaite Konstancija , Yu Zhaohua , Wang Chunliang , Cao Qiran , Soderberg Per
Published: January 2025

Aims/Purpose: To compare measurements of circumpapillary Retinal Nerve Fiber Layer Thickness (cpRNFLT) and Pigment epithelium central limit Inner limit of the retina Minimal Distance (PIMD), respectively, between healthy and glaucoma eyes with regard to angular distribution of the measurements in the frontal plane and the variation coefficients for measurements of cpRNFLT‐2π and PIMD‐2π.

Methods: 17 eyes without ocular pathology and 7 with glaucoma, each from a different subject, were included. In each eye, the ONH was captured in 3 iterated volumes at one occasion with the OCT‐Triton (Topcon, Japan). In each volume, the nerve fiber layer thickness was resolved in 12 frontal plane clock hrs as cpRNFLT with the Topcon software, and as PIMD with an automatic custom‐made software. Finally, the 12 clock hrs were averaged and the inter‐volume errors were determined with ANOVA for comparison of variation coefficients (CV:s) between cpRNFLT‐2π and PIMD‐2π.

Results: PIMD‐2π was approximately 3 times higher than cpRNFLT‐2π in the healthy eyes and 2.5 times higher in the glaucoma eyes. In both groups, PIMD peaked superiorly and inferiorly, slightly shifted nasally, and cpRNFLT peaked superiorly and inferiorly, slightly shifted temporally. The CV for iterated measurements at the same occasion was slightly higher for PIMD‐2π than for cpRNFLT‐2π in the healthy eyes, and of the same order for PIMD‐2π and cpRNFLT‐2π in the glaucoma eyes.

Conclusions: PIMD‐2π and cpRNFLT‐2π were lower in glaucoma‐ than in healthy eyes, probably due to less ganglion cell axons. PIMD‐2π was generally 2.5‐3 times higher than cpRNFLT‐2π. The CV:s were on the order of 1.5‐2.5 x10‐2 for both healthy‐ and glaucoma eyes and both quantities measured. Thus, averages of 3 volumes at each occasion is sufficient for comparison of measurements among occasions within subjects.
Automated analysis of retinal vascular features, age, sex and disc size in a large cohort of primary open angle glaucoma patients
Authors: Van Eijgen Jan , Fhima Jonathan , Reiner‐Benaim Anat , Beeckmans Lennert , Abramovich Or , Stalmans Ingeborg , Behar Joachim A.
Published: January 2025

Aims/Purpose: Deriving vascular features of retinal images is a proposed noninvasive method to assess vascular health. Although several studies have linked cardiovascular risk to retinal image features, they often rely on limited datasets or have used deep learning approaches with limited explainability. This research introduces an end‐to‐end method for analyzing the retinal vasculature in large retinal image datasets, applied for primary open angle glaucoma (POAG).

Methods: 115,237 retinal images of the UZ Leuven Glaucoma Clinic were extracted. 4858 unique images remain of POAG patients (n = 3010) and controls (n = 1848) after image quality assessment, optic disk detection, region of interest definition, automated segmentation of arterioles and venules (LUNet algorithm), and parametrization of the vascular biomarkers (PVBM toolbox). Analysis of covariance and linear mixed models were used to adjust for age, sex and disc size.

Results: Both arteriolar and venular diameter, area, length, tortuosity, branching angle, endpoints, intersection points and both mono‐ as multifractal dimension levels are independently lower in POAG patients and older patients (all p < 0.001), after adjustment for sex, disc size and multiple testing. The multivariate linear mixed models additionally show that the vascular features are significantly influenced by sex and disc size, which necessitates correct adjustment.

Conclusions: This is the first time a fully automated end‐to‐end pipeline is published for the analysis of retinal vascular geometry in a large cohort (n = 4858). Given the independent similarities in retinal vascular geometry changes between older age and POAG prevalence the theory of pronounced vascular ageing in POAG patients is proposed. This novel approach enables quantitative analysis of eye vasculature and supports the study of its correlation with specific diseases, facilitating reproducible analysis of large datasets and providing explainability to deep learning approaches.
VOGT triad: A classic but rare sequel of acute angle closure glaucoma
Authors: Younes Laarif , Nihal El Arari , Salma Hamidi , Ouadghiri Soukayna , Benchekroun Saad , Elhachimi Rim , Abdellah Amazouzi , Oufae Cherkaoui Lalla
Published: January 2025

Aims/Purpose: We report a case of a 62 year old woman with history of multiple episodes of acute painful red eye over the past 2 years presenting to the consultation for visual acuity decrease since 1 year ago.

Methods: The best corrected visual acuity was 3/10 OD and count fingers OG with a mild conjunctival hyperemia,clear cornea,a very shallow anterior chamber centrally and peripherally.The IOP was 26mmHg OD and 28mmHg OS and the left eye presented with nuclear sclerosis grade 2 with multiple glaucomaflecken( anterior sub‐capsular opacities),iris peripupilary atrophy patches extending from 12 hour to 8 hour and a slightly dilated sluggish pupil realizing the classic but rare vogt triad.Goniscopy found in OS a 360° closed angle with anterior peripheral synechiae over 270°.The fundus revealed a complete optic nerve excavation in the left eye.

Results: The patient was diagnosed with chronic angle closure glaucoma complicating multiple undiagnosed acute angle closure glaucoma and started on prostaglandine analogues monotherapy then bitherapy with a good IOP control(14 mmHg and 17 mmHg).

Conclusions: Vogt triad is found as a sequel of acute angle closure glaucoma and contains glaucomaflecken who are anterior subcapsular lens opacities secondary to ischemia,peripupilary iris patches of atrophy and sluggish pupilary reaction due to iris sphincter ischemia.

It is rarely complete and can only be found in non diagnosed,neglected and repeated acute angle glaucoma closure.

References

Bharathi, Shabana. Vogt's triad – Do we find the triad all the time?. Indian Journal of Ophthalmology ‐ Case Reports 3(2):p 584‐585, Apr–Jun 2023. | DOI: 10.4103/IJO.IJO_2511_22
Modulation of post‐surgery fibrosis in glaucoma filtration surgery by targeting retinoic acid signaling
Authors: Wang Xiaomeng , Wong Tina , Anjali Rajakrishna , Lim Seok Ting
Published: January 2025

Aims/Purpose: Glaucoma filtration surgery (GFS) aims to alleviate intraocular pressure by improving fluid drainage from the eye. However, post‐surgery scarring, particularly around the surgical site, can impede fluid flow and compromise surgical outcomes. Dysregulated inflammatory responses and abnormal extracellular matrix (ECM) remodeling contribute to excessive scarring. Retinoic acid signaling is known to modulate immune responses, ECM remodeling, and fibrosis in various organs. This study seeks to investigate the influence of key retinoic acid signaling components on post‐surgery scarring in the eye.

Methods: Expression levels and patterns of selected retinoic acid signaling pathway components were assessed in conjunctival tissues of C57BL/6 mice undergoing GFS using RT‐PCR and Western blot analysis. Mice with global deletion of specific retinoic acid signaling pathway components underwent GFS to evaluate their role in subconjunctival fibrosis. Inflammatory responses were evaluated by immunofluorescence staining for the pan‐myeloid marker CD11b, and fibrotic tissue was visualized using Masson's trichrome stain. Subconjunctival tissues from knockout and wild‐type littermate controls were analyzed for inflammatory cytokines, chemokines, and fibrotic markers via Western blot analysis.

Results: GFS induced the expression of different components of the retinoic acid signaling pathway in mice. Deletion of specific retinoic acid signaling pathway components resulted in alterations in GFS‐induced recruitment of myeloid cells and ECM remodeling.

Conclusions: Modulating retinoic acid signaling presents a promising approach for controlling post‐surgery fibrosis in the eye, offering an alternative avenue to enhance the outcomes of glaucoma filtration surgery.
Evaluation of the conjunctival bacterial flora in the New Zealand white rabbit
Authors: Cejudo Raquel Maroto , Encalada Denisse Michelle Espinosa , Rodriguez Oscar Esparcia , Sango Mónica Gómez‐Juarez , Pretel Fernando Andrés , Valenciano Carlos Cava
Published: January 2025

Aims/Purpose: We aimed to characterize the normal bacterial flora of conjunctiva and eye lids of the white New Zealand rabbit.

Methods: Twelve rabbits (Twenty‐four eyes) were employed. Before sampling, an ophthalmological examination of the ocular surface was performed to exclude the presence of any lesions.

Microbiological sampling by sterile swabs was performed on the superior and inferior conjunctival fornix. Samples were placed in eSwab 1 mL transport medium (eSwab® ‐ Copan's Liquid Amies Elution Swab) and submitted for culture. They were cultured on blood agar, chocolate agar and sabouraud agar. Species identification was carried out by mass spectrophotometry (MALDI‐TOF, BioMèrieux®) and/or conventional techniques. They were seeded in triplicate and the quantification of the germs was expressed in terms of CFU/mL.

Results: Seven different species were observed. The most frequent was Moraxella cuniculi (705 ±1129 CFU/mL), followed by Corynebacterium spp (71.43 ±267.3 CFU/mL) and coagulase negative Staphylococcus (5 ±10.92 CFU/mL). Other less frequently species observed were Staphylococcus aureus, Streptococcus viridans, Tsukamurella spp and Bacillus spp.

Statistical analysis showed a significant statistical difference between M. cuniculli and the other species observed. (Krussal Wallis p < 0.001)

Conclusions: M. cuniculi was the species with the highest CFU/mL in the conjunctival flora of the rabbit.
Increasing myopia post‐COVID: Evidence from child vision screening age 3.5 to 5.5 years in Scotland
Authors: Evans Bruce , Pentland Lee , Edgar David , Shah Rakhee , Evans Benjamin , Conway Miriam
Published: January 2025

Aims/Purpose: Scotland's child vision screening by orthoptists at 3.5‐5.5 years is taken up by ~85% (40,000‐50,000 annually). Screening failures are referred for eye examinations, including cycloplegic refraction. Aim 1: report refractive error data from these examinations (5,000‐7,000 annually) for 3 years pre‐ and 2 years post‐COVID. Aims 2 and 3: investigate correlations between myopia and socio‐economic deprivation and urban/rural dwellings.

Methods: Right eye spherical equivalent refraction (SER) data from 10 Health Boards (HB) were compared. Population proportions within each deprivation index quintile (DIQ) and living in different dwelling types are known for each HB. Associations were investigated between these variables and proportions of children in each HB who failed screening and were found to have myopia.

Results: Frequency distributions revealed a myopic shift in SER post‐COVID. Median SER (IQR) was in 2013‐14 +1.25D (+0.50 to +2.63); 2014‐15 +1.38D (+0.38 to +2.50); 2015‐16 +1.38D (+0.50 to +2.63); 2020‐21 +1.13D (+0.25 to +2.25); 2021‐22 +1.25D (+0.37 to +2.25). Statistically significant findings: overall difference between years (Kruskal‐Wallis, p < 0.0005); pairwise comparisons (p < 0.0005) between each of the first 3 years and each of the last 2 years; but not (p > 0.66) in pairwise comparisons of 2013‐16 or of 2020‐22. The proportion of children with myopia (≤‐0.50D): < 8% annually 2013‐16, 12% in 2020‐21, 11% in 2021‐22. There was a linear trend for an increasing proportion with myopia (r2 = 0.94, p = 0.006). Correlations between the proportions of children in each HB with myopia and who fell within each DIQ were low (r2 < 0.33). There was a high positive correlation (r2 = 0.83, p = 0.002) between the proportion with myopia and proportion of dwellings that were flats/apartments.

Conclusions: The proportion with myopia has increased post‐COVID. A strong association exists between living in flats/apartments and myopia, but no strong correlation with a deprivation index.
Impact of decreased fetal hemoglobin fraction on the development of retinopathy of prematurity
Authors: Fevereiro‐Martins Mariza , Aguiar Laura , Inácio Ângela , Cardoso Carlos , Santos Ana Carolina , Teixeira Filipa , Rosa Rita , Parreira Ricardo , Barros Pedro , Teixeira Susana , Mota Mafalda , Monteiro Madalena , Alfaiate Mário , Silva Renato , Breda Jorge , Guimarães Hercília , Marques‐Neves Carlos , Pinto Rui , Bicho Manuel
Published: January 2025

Aims/Purpose: To evaluate the potential of fetal hemoglobin (HbF) as a predictor biomarker of the development of retinopathy of prematurity (ROP).

Methods: Multicenter, observational, and prospective study of preterm newborns (PTNB) from eight Portuguese neonatal intensive care units born with gestational age (GA) < 32 weeks or birth weight (BW) < 1500 grams. ROP staging followed the International Classification of ROP (ICROP). Sociodemographic, clinical, and surplus blood after routine laboratory tests were collected. HbF levels were measured in the first 4 weeks of life using standardized methods. PTNB were divided into two groups based on ROP development: ROP or no ROP. Statistical analysis used SPSS with a significance level of p < 0.05.

Results: 82 PTNB were included, with GA mean of 28.1±2.1 weeks, BW mean of 1055.8±258.3 grams, and 41 (50.0%) were female. Among PTNB, 29 (35.4%) developed ROP: 12 (14.6%) had stage 1, 10 (12.2%) stage 2, and 7 (8.5%) stage 3. Four (4.9%) PTNB required treatment: 2 (2.4%) with laser photocoagulation and 2 (2.4%) with anti‐VEGF.

PTNB with ROP had statistically more red blood cell transfusions in the first 4 weeks of life than those without ROP (0 transfusions: 8 (27.6%) vs 43 (81.1%); 1 or 2 transfusions: 13 (44.8%) vs 9 (17.0%); 3 or 4 transfusions: 8 (27.6%) vs. 1 (1.9%); p < 0.001), even adjusting for GA (p = 0.009).

PTNB with ROP had statistically lower HbF percentages than infants without ROP (median 62.7% (min. 31.3% – max. 85.1%) vs median 77.3% (min. 32.0% – max. 97.7%); p < 0.001) even adjusting for GA (p = 0.003). The Kaplan‐Meier survival curves reinforce these results, where PTNB groups with lower HbF percentages had a significantly higher probability of developing ROP (groups divided by the median: p < 0.001; groups divided by quartiles: p < 0.001).

Conclusions: Our findings suggest that the reduction in HbF within the first four weeks of life may serve as an early and cost‐effective predictive biomarker for the development of ROP.
Archetypal analysis for visual field loss characterization of leber hereditary optic neuropathy
Authors: Coutinho Catarina , Zanchetta Ferdinando , Carbonelli Michele , Galzignato Alice , Battista Marco , Fantaguzzi Federico , Amore Giulia , Carelli Valerio , Brotto Luigi , Nucci Paolo , Checchin Lisa , Savini Giacomo , Bandello Francesco , La Morgia Chiara , Cascavilla Maria Lucia , Fioresi Rita , Barboni Piero
Published: January 2025

Aims/Purpose: Characterization of Visual Field (VF) loss patterns of chronic stage Leber Hereditary Optic Neuropathy (LHON) patients by application of machine learning (ML).

Methods: For chronic stable LHON patient, at least 2 years after disease onset, 24‐2 and 30‐2 VFs tests performed by SITA standard Humphrey VF analyzer (Carl Zeiss Meditec) were collected. Two groups were considered: with visual acuity (VA) recovery, when a change of more than 0.2 decimal or from off‐chart to on‐chart vision after initial loss of vision; and without VA recovery. Resorting to Python, archetypal analysis (AA) was implemented to each group using the VFs total deviations (TDs). Spearman correlations were performed between each archetype (AT) relative weight and the VFs mean deviation (MD).

Results: From 117 patients (203 eyes), 104 VFs made up the Recovered Group, and 115 VFs the Not Recovered Group. Both AA models were made up of 7 ATs. For the Recovered Group, the normal VF AT had the highest weight (33.40%), followed by different severity central scotoma ATs (AT2, 16.32%; AT3, 11.82%; AT5, 10.37%). For the Non‐Recovered Group, first the widespread loss AT (47.87%), followed by enlarged central scotoma ATs (AT2, 11.13%; AT5, 8.97%). For the Recovered Group, AT3 (Cecocentral Scotoma), AT4 (Fenestration) and AT6 (Widespread loss) weights decreased with increasing MD; and AT1 (normal VF) and AT5 (Central Scotoma) increased with increasing MD. The AT1 (Widespread Loss) weight of the Non‐Recovered Group decreased with increasing MD, while AT5 (Enlarged Central Scotoma) weight increased with increasing MD.

Conclusions: Implementation of AA‐ML allowed the association of more severe and widespread visual loss patterns to LHON patients without visual recovery, whereas less severe and more centralized patterns to recovered patients, as expected. Therefore, the presented VF analysis might present as a standardized method for LHON visual loss characterization, providing further characterization of patients with and without vision recovery.
Distribution and associated factors of keratometry and corneal astigmatism in general elderly population
Authors: Nabovati Payam , Hashemi Alireza , Aghamirsalim Mohamadreza , Hashemi Hassan , Khabazkhoob Mehdi
Published: January 2025

Purpose: To determine the distribution and associated factors of keratometry and corneal astigmatism in people aged 60 years and above.

Methods: In this cross‐sectional study, 160 clusters were randomly selected from Tehran city (Iran) using the multi‐stage cluster sampling method. All participants underwent optometric examinations including testing uncorrected and best‐corrected distance visual acuity, non‐cycloplegic autorefraction, and subjective refraction. Pentacam imaging for all participants was carried out using Pentacam AXL. Keratometry and corneal astigmatism were reported based on Pentacam's data.

Results: 4244 eyes from 2268 individuals were analyzed. The average, standard deviation and 95% confidence interval of flat keratometry, steep keratometry, mean keratometry, and corneal astigmatism were 44.02±1.58 diopters (95% confidence interval: 43.94 to 44.1), 44.86±1.67 diopters (95% confidence interval: 44.78 to 44.94), 44.44±1.58 diopters (95% confidence interval: 44.36 to 44.52), and 0.84±0.74 diopters (95% confidence interval: 0.81 to 0.87), respectively. According to the multiple generalized estimating equation model, the mean keratometry was significantly higher in males, in myopes, and in those with higher systolic blood pressure. Moreover, the mean keratometry was inversely related to the axial length, height, anterior chamber depth, corneal diameter, and central corneal thickness. The prevalence of various types of corneal astigmatism > 0.50 diopters was as follows; with‐the‐rule: 32.5%, against‐the rule: 18.2%, and oblique: 10.0 %.

Conclusions: The present study investigated the normal distribution of keratometry and corneal astigmatism in elderly, and results can be used in clinical matters, especially in intraocular lens power calculation. Sex and some biometric components such as anterior chamber depth, corneal diameter, and central corneal thickness are significantly related to keratometry.
Clinical characteristics of post‐refractive surgery corneal ectasia
Authors: Son Yengwoo , Jeon Hyun Sun
Published: January 2025

Aims/Purpose: The aim of this study was to explore the clinical characteristics, visual acuity (VA), and topographic patterns in patients who developed corneal ectasia (CE) following myopic laser vision correction (LVC).

Methods: We conducted a retrospective review of medical records for patients diagnosed with CE after laser vision correction between 2009 and 2023 at a tertiary hospital in Korea. We collected various data, including patient demographics, medical history, the type of refractive surgery and postoperative periods., VA at their initial and final visits, refractive errors, and topographic biometric data.

Results: In total, 36 eyes of 28 patients (13 females and 15 males) were included, and 8 (28.5%) cases were bilaterally involved. The most common type of surgery was LASIK (24 patients, 85.7%), while the remaining patients underwent LASEK (3 patients, 10.7%) or PRK (1 patient, 3.6%). In unilaterally involved eyes (20 eyes), VA, spherical equivalent (SE), and astigmatism of CE‐affected eyes were significantly different from those of eyes with uninvolved eyes (all p < 0.001). In eyes with over 12 months of follow‐up observation (12 eyes of 9 patients), no significant progression was noted in VA (p = 0.392), SE (p = 0.675), astigmatism (p = 0.737), and topographic parameters.

Conclusions: CE can develop even after comprehensive preoperative screening following LVC. This condition can significantly impact patients' quality of life by substantially reducing VA. Moreover, considering the spectrum of diseases that keratoconus represents, there is a possibility that CE may cease to progress after a certain age. Further investigations are required to understand the progression of CE concerning age in affected patients.
Identifying factors associated with perfluorohexyloctane treatment response in dry eye disease patients with meibomian gland dysfunction: A post‐hoc analysis
Authors: Zhu Lei
Published: January 2025

Aims/Purpose: The heterogeneous nature of dry eye disease (DED) associated with meibomian gland dysfunction (MGD) poses challenges for effective treatment, necessitating a deeper understanding of associated factors. Perfluorohexyloctane eye drops (PED, SHR8058) have shown efficacy in DED treatment, yet variability in treatment response remains unclear. This post‐hoc analysis explores factors associated with PED treatment response to identify patient subgroups benefiting most.

Methods: Using data from a phase 3, randomized, double‐blind, salinee‐controlled, multicenter clinical study (NCT05515471), this post hoc responder analysis aggregated data from 156 patients in the PED treatment group. Response outcomes for signs and symptoms were assessed using total corneal fluorescein staining (tCFS, ≥ 3 reductions from baseline) and eye dryness score (EDS, ≥ 30% reduction from baseline), respectively. Univariate and multivariate logistic regression using stepwise selection method, with the cutoff p‐value to enter of 0.1 and stay in the model set at 0.05 were applied to explore potential variables associated with response outcomes.

Results: Among 156 patients treated with PED, the mean (SD) of tCFS and EDS was 6.2 (1.9), and 64.7 (15.1) at baseline. In both univariate and multivariate regression analysis for signs response, tCFS score and ametropia showed association with signs response (odds ratio [OR] 1.4; 95% confidence interval [CI], 1.08‐1.73 and OR 3.0; 95% CI, 1.27‐7.25 respectively in multivariate analyses). Regarding symptoms, EDS (OR 1.1; 95% CI, 1.02‐1.11), awareness of DED symptoms (OR 1.0; 95% CI, 0.93‐0.99), dryness frequency (OR 1.0; 95% CI, 0.93‐1.00), and tCFS (OR 1.4; 95% CI, 1.05‐1.77) were independent associated factor of EDS in multivariate analysis.

Conclusions: These post hoc findings suggest that tCFS score, ametropia, EDS, awareness of DED symptoms and dryness frequency are associated with PED treatment response.
Visualizing morphological features of diseases of the corneal endothelium
Authors: Dallinga Marchien , van der Krogt J. M. A. , van der Meulen I. J. E. , Murphy C. C. , van Buul J. D.
Published: January 2025

Aims/Purpose: To study several corneal endothelial diseases in order to find a set of morphological characteristics for each disease.

Methods: Human cornea samples were collected from patients receiving a corneal transplant that involved the endothelium. Samples were fixed and immunofluorescently stained using antibodies against the nucleus, actin cytoskeleton, Beta‐catenin and the ZO‐1 junctional protein. Images were analyzed and variation in cell size and percentage of hexagonal cells were compared to in vivo specular microscopy to validate the staining methods. Images were then further analyzed to find new characteristics for the different diseases.

Results: Samples were collected from patients with healthy endothelial cells, Fuchs’ endothelial corneal disease, Pseudophakic bullous keratopathy, rejection of a previous corneal graft, failed corneal graft, inflammatory corneal melt and congenital hereditary endothelial dystrophy. A set of parameters for each disease was established which included newly described features such as leukocyte transendothelial migration, morphology of the interdigitations on the basal surface of the cells and the presence of multinucleated cells.

Conclusion: We have established morphological parameters for several diseases affecting the corneal endothelium. These can be used for further studies into the pathological mechanisms of each disease and possibly in the development of future therapies.
Topical sevoflurane role as antiseptic on normal conjunctival flora in a rabbit model
Authors: Encalada Denisse Michelle Espinosa , Cejudo Raquel Maroto , Rodríguez Óscar Esparcia , Sango Mónica Gómez Juárez , Pretel Fernando Andrés , Valenciano Carlos Cava
Published: January 2025

Aims/Purpose: To assess the antiseptic properties of Sevoflurane (SF) when topically applied to the ocular surface in an animal model, and to compare the results with that of 5% Povidone Iodine (PY), a commonly used ophthalmic antiseptic.

Methods: This randomized clinical trial involved 24 eyes from 12 New Zealand white rabbits, which were divided into two groups: SF (n = 12) and PY (n = 12), based on the substance administered. Prior to the application of any agent, baseline samples were collected from the conjunctival sac of each eye to determine the normal conjunctival flora. Subsequently, a single dose of 0.1 mL of either SF or PY was administered according to the group allocation. Conjunctival sac samples were then taken at 5 and 30 minutes post‐application. The collected samples were subjected to microbiological analysis.

Results: At the commencement of the study, Moraxella cuniculi was identified as the predominant species, with a statistically significant higher colony‐forming units per milliliter (CFU/mL) compared to other species (p < 0.001). In the SF group, there was a statistically significant reduction in CFU/mL for both Moraxella cuniculi and Staphylococcus aureus following treatment. Conversely, in the PY group, a significant reduction was observed only for Moraxella cuniculi. Comparative analysis between the SF and PY groups revealed no statistically significant differences in the reduction of CFU/mL for Moraxella cuniculi at any time point during the study (p > 0.05).

Conclusions: Topical application of SF effectively reduces the CFU/mL of predominant germs on the ocular surface of albino rabbits, yielding results comparable to those achieved with PY.
The analysis of miR‐133b and miR‐122 in cord blood for eye drop preparations. The differential contribution of platelet‐rich‐plasma and serum
Authors: Ciavarella Carmen , Bergantin Elisa , Buzzi Marina , Versura Piera
Published: January 2025

Aims/Purpose: Cord blood (CB) –derived eye drops are safe and effective in many ophthalmological diseases, primarily persistent keratopathy related to severe dry eye disease. MicroRNA (miRNA) fine tune multiple messenger RNAs (mRNAs) and modulate several pathological pathways. This study was aimed at comparing platelet‐rich plasma (PRP) and serum (S) from CB, for expression of miR‐133b and miR‐122, negative regulators of inflammation and neuropathic pain respectively.

Methods: PRP and S prepared from the same CB donor (n = 6) were processed for miRNA extraction, subjected to miRNA specific Reverse‐Transcription and Pre‐amplification. MiRNA analysis was performed by Real Time PCR and Digital Droplet PCR, (ddPCR) comparing the two approaches in terms of yield and data comparability. Small nuclear RNA U6 and RNU44 were used as housekeeping genes.

Results: PRP samples displayed higher yield in terms of RNA amount and purity than serum (mean RNA concentration: 30 ng/ul vs 8 ng/ul, respectively). The snU6 was more stable among all samples and was selected as housekeeping gene. miR‐133b was 26% lower in S than in PRP, whereas miR‐122 did not show significant differences between CB and S. ddPCR data were comparable with Real Time analysis, displaying higher sensibility also in samples with lower RNA yield.

Conclusions: According to our data, CB preparations contain miRNA involved in the modulation of inflammatory process and pain in ocular surface diseases. PRP and S share similar expression levels of miR‐122, whereas miR‐133b is higher in PRP, indicating that PRP is more powerful in terms of anti‐inflammatory function than S, whereas both CB preparations contribute to ameliorating pain in ocular surface diseases. Further investigations are addressed at increasing the CB sample number to dissect the miRNA: mRNA network and validate the miRNA analysis by ddPCR, for a more accurate quantification in view of the therapeutic applications of CB preparations.
Building a framework for public and patient involvement in dry eye disease research. A case study
Authors: Ames Tess , Reynolds Alison , Matthews Evan , Golestenah Dorsa , Sarfraz Muhammad , Gooney Martina , Kinsella Sharon , Logan Ann , Lynch John , McLoughlin Peter , O'Donovan Orla , O'Reilly Niall , Rani Sweta , Filipe Helena Prior , Fitzhenry Laurence
Published: January 2025

Aims/Purpose: This study aims to improve bidirectional communication strategies between patients/public, preclinical researchers, and clinical experts to address the lack of effective public and patient involvement (PPI) in preclinical vision research, aiming to refocus research on actual patient needs.

Methods: An international team conducted multiple PPI activities, including a critical review on PPI in preclinical ocular research1, World‐café workshops, patient interviews, structured surveys, and round‐table discussions. Dry Eye Disease's wide clinical presentation and impact on daily life were explored. Patient experiences were shared to better understand their needs, increase research value, awareness, and advocacy.

Results: Activities highlighted the need for incorporating PPI in ocular research at the preclinical stage. Recurrent themes were identified across patients and researchers. From 20 patient interviews and 50 surveys, 82% responded that they received most information from clinical spaces and were unaware of current research.2 Patients did not know how to become involved in PPI. In a PPI Training Course, 19 preclinical researchers agreed on the need for clearer PPI guidelines and training.

Conclusions: PPI activities emphasized DED's severe impact on QoL and the need for new treatments. Round‐table discussions fostered connections and deeper understanding of DED, shifting researchers' focus to unmet patient needs. Further integration of PPI into preclinical research will benefit both researchers and patients. This multimodal PPI approach can benchmark incorporating patient perspectives in preclinical ocular research. Next steps – with patients, create a tool kit for communications skills development for pre‐clinical researchers.

References

Ames T, Matthews E, Reynolds A et al. How patient/public involvement impacts the research journey – an overview of the visual impairment research field, Open Res Europe 2023, 3: 135. https://doi.org/10.12688/openreseurope.16057.1.

Ames T, Matthews E, Reynolds A et al. ARVO. 2024. Dry Eye Disease as a case study to understand the public and patient involvement gap in lab‐based preclinical vision research using interdisciplinary approaches [Poster].
Computational and experimental mechanical characterization of a novel corneal implant for the treatment of keratoconus
Authors: Ragonese Graziana Maria , Carbonaro Dario , Zambon Sara , Villa Elena , Grosso Edoardo , Kakanga Moses , Lepore Emiliano , Gallo Diego
Published: January 2025

Aims/Purpose: Current treatment options of keratoconus have several limitations. These limitations have been addressed by developing a novel nitinol GROSSO® implant, that restores the physiological curvature of the cornea by virtue of a dome‐shaped design. Its minimally invasive implantation requires accurate assessment of the mechanical properties, investigated here both experimentally and computationally.

Methods: Bending of two opposite edges of the implant is necessary for its implantation in the intracorneal pocket. Bending was conducted experimentally at 37°C using a DMA Q800 (TA Instruments) with a thermal chamber and a cell load of 18 N to obtain force‐displacement curves. A computational model of the real implant was reconstructed from microcomputed tomographic acquisitions (Phoenix v|tomo|x m, resolution: 1μm). The mechanical behaviour of the implant was modelled by implementing a superelastic constitutive law with material parameters obtained from experimental tensile tests of the nitinol, which also determined the plastic permanent deformation value. Finite element analysis of the bending simulation was performed in Abaqus (Dassault Systèmes Simulia Corp.) to obtain the bending force (BF) and assess the absence of permanent deformation.

Results: A good agreement between the experimental (0.09 N) and computational tests (0.08 N) in terms of BF was observed. The computational simulation highlighted that the maximum principal strain value during bending was 10.8%, i.e. below the limit strain for plasticity of 12%.

Conclusions: The GROSSO® implant can be safely bent during implantation with minimal effort, as the force applied does not exceed 0.1 N. The ongoing validation of the computational model will enable a cost‐effective prediction of macro‐scale mechanical properties and compliance with relevant standards and regulatory requirements. Additional critical scenarios and the remodeling effect imposed by the implant on corneal tissue will be the subject of future investigations.
Anterior segment optical coherence tomography assisted analysis of characteristics of graft dehiscence after descemet membrane endothelial keratoplasty for failed penetrating keratoplasty
Authors: Mestanoglu Mert , Vishwakarma Pratima , Welge‐Lüßen Veronika , Schlereth Simona , Cursiefen Claus , Bachmann Björn
Published: January 2025

Aims/Purpose: To analyze anterior segment optical coherence tomography (AS‐OCT) parameters of graft dehiscence after Descemet membrane endothelial keratoplasty (DMEK) performed due to graft failure post penetrating keratoplasty (PK).

Methods: All cases with available AS‐OCT images after DMEK performed due to previously failed PK graft were retrospectively analyzed. In total 142 dehiscences after DMEK in 75 eyes could be identified. The size, depth, location of dehiscence and its correlation between presence of graft‐host interface (IF) override and presence of step at the IF was assessed.

Results: Majority of the patients were male (58.7%) and average age at presentation was 67 ± 13.6 years. Multiple areas of dehiscence were noted in 49.3% of eyes. Rebubbling was required once in 72% and multiple times in 24% cases. Dehiscence was noted to cross over the IF in 53.5%. Steps at the IF was noted in 41.5%, and 22.5% of the dehiscences with step crossed the IF. No significant difference was noted when median depth and size of the dehiscences crossing over the IF were compared with those not crossing over the IF (p = 0.268 and p = 0.206, respectively). Comparison between the median depth and size of the dehiscences crossing over the IF with presence and absence of step showed no significant difference (p = 0.23 and p = 0.196, respectively). Also, presence and/or size of step at the IF did not have a significant effect on depth, size and incidence of dehiscence.

Conclusions: In our study, dehiscence of DMEK grafts occurred in close vicinity to the PK graft‐host interface. However, size and depth of the dehiscence were not affected by crossing of the dehiscence over the graft‐host junction interface. Also, presence of step and its size did not seem to affect the depth, size and incidence of the dehiscence. Our evaluation suggests that the edge of the DMEK graft should have a distance to the PK interface, independent of the regularity of the PK graft‐host junction.
Success rate of primary cultures of corneal endothelial cells from donors over 50 years old
Authors: He Zhiguo , Aouimeur Inès , Sagnial Tomy , Louise Parveau , Perrache Chantal , Thuret Jean‐Yves , Gain Philippe , Thuret Gilles
Published: January 2025

Aims/Purpose: Due to the global shortage of corneal donors, alternatives such as cell injection therapy and tissue‐engineered endothelial keratoplasty are being developed. These methods require mass production of corneal endothelial cells (CECs), which is challenging, especially with corneas from "regular" donors (aged around 70 on average in Europe). Notably, the first clinical successes reported by Kinoshita et al. used corneas from donors under 29, which are rare. This study aims at investigating the success rate and specific challenges of primary cultures of CECs from older donors.

Methods: An analysis was conducted on the primary culture of CECs from 127 organ‐cultured (OC) corneas. The average donor age was 74 ± 13 years (range 50‐96), with a postmortem (PM) duration of 15 ± 7 hours (range 1‐27), initial endothelial cell density (ECD) of 2280 ± 567 cells/mm2 (range 1060‐3536), and an OC time of 29 ± 21 days (range 1‐90). Cell cultures were classified as successful or failed based on cell morphology and ECD. A successful culture was defined by typical CEC morphology and ECD ≥ 2000 cells/mm2 at the third cell passage or later.

Results: Successful cell cultures were achieved from 13 corneas (10.2%). The characteristics of these 13 corneas were: average age 74 ± 15 years (range 52‐96), PM duration 14 ± 7 hours (range 1‐24), initial ECD 2416 ± 523 cells/mm2 (range 1287‐3248), and OC time 23 ± 17 days (range 4‐56). No significant differences in these characteristics were found between successful and failed cultures. Among the failed cultures, 63.9% had lower ECD, 26.2% exhibited endothelial to mesenchymal transition (EndMT), and 9.9% displayed both failure features. Different wells from the same cornea sometimes showed different cell features.

Conclusions: Primary culture of CECs from older donors is feasible but has a low success rate (10%). No correlations were found between the success of cultures and corneal characteristics, suggesting the influence of random, poorly understood factors likely related to the culture method. Optimizing the culture method is essential to improve the success rate and facilitate industrial application.
Morphometric histological description of fuchs endothelial dystrophy guttae
Authors: Jonas Rahul , Howaldt Antonia , Matthaei Mario , Schlereth Simona , Bachmann Björn , Cursiefen Claus
Published: January 2025

Aims: Morphometric histological description of Fuchs corneal endothelial dystrophy guttae as well as anterior banded and posterior layer of Descemet's membrane

Methods: After routine DMEK procedures, 47 consecutive explants were taken for histopathological examination as part of clinical routine from 38 patients. 6μm thick sections were cut and stained with PAS and HE. The morphometric analysis was done using a Leica DM‐2500 microscope. Guttae were counted in a line measuring 400μm randomly selected in the middle of the tissue. The largest guttae with the best cross section was used to measure height and width at the base, the middle and the top. The anterior banded layer (ABL) and the posterior (banded and non‐banded as one) layer (PL) were measured below that gutta. The endothelial cells closest to that gutta were measured to get the height and width. Measurements were done using Discus Software (Ingenieursbüro Hilgen). Statistical analysis was done using linear regression on SPSS (Version 29.0 IBM).

Results: The mean amount of guttae in the 400μm section was 11.76 ± 4.8. The mean thickness of ABL was 2.92 ± 0.96μm and of PL 8.59 ± 2.7μm. The guttae measured in height 8.68 ± 2.99μm, in width (base) 14.55 ± 4.22μm, in width (middle) 13.13 ± 4.54μm and in width (top) 14.72 ± 4.69μm. The endothelial cells measured in height 3.28 ± 0.98μm and in width 8.02 ± 2.8μm. The width (middle) of the guttae correlated with the width (base) (p < 0.001), width (top) (p < 0.001) and the width of the endothelial cells (p = 0.041). The PL correlated with the height of the guttae (p = 0.028), which also correlated with the height of the endothelial cells (p = 0.044). The width (top) correlated, additionally to the width (middle), with the width of the endothelial cells (p = 0.031). The PL did not correlate with the age of the patients. Most of the correlations kept their statistical significance after Bonferroni correction.

Conclusions: The thicker the PL was, the higher were the guttae (r2 = 0.14). The wider the width (base) was, the wider the width (top) (r2 = 0.209) and width (middle) (r2 = 0.455) was. Considering the observed variability in corneal guttae shape and dimensions even at the same corneal location at, there might be differences in the pathophysiological processes warranting further analysis.