bluuebunny/crossref_metadata_2025 huggingface dataset:
Optical coherence tomography findings in persistent hyaloid artery: A prospective study
Authors: Sakji Fatma , Aoun Safa Ben , Maamouri Rym , Ferchichi Molka , Fendouli Ines , Cheour Monia
Published: January 2025

Aims/Purpose: To describe the features of peripapillary persistent hyaloid artery and its effects on disc parameters using Swept‐source optical coherence tomography (SS‐OCT) and SS‐OCT angiography (SS‐OCT A).

Methods: Seven eyes of 7 patients diagnosed with Persistent hyaloid artery were prospectively reviewed at the department of Ophthalmology in the Habib Thameur Hospital, Tunisia, between January 2024 and June 2024. All patients were assessed for peripapillary retinal nerve fibers layer (pRNFL) thickness by SS‐OCT, and blood flow by papillary OCT‐A, 4.5 mm*4.5 mm cubes.

Results: Mean age was 36.33 years, with 4 women and 3 men. SS‐OCT showed peripapillary hyperreflective tubular material of the persistent hyaloid artery in the right eye of 3 patients and in the left eye of 4 patients. On analysis of the pRNFL thickness, the mean average thickness was 110.8, Inferior quadrant (150.8), superior quadrant (134), nasal quadrant (83.4) and temporal quadrant (74.8). pRNFL were thickened in one eye, altered in one eye in the superior quadrant, and preserved in five eyes. SS‐OCT A revealed no blood flow at the lesion in all eyes.

Conclusions: A persistent hyaloid artery is an uncommon lesion whose diagnosis, evaluation and monitoring have become easily possible using SS‐OCT and SS‐OCT A. Evaluating the vascular flow at the level of the optic nerve head would be of great importance in order to prevent certain complications, notably vitreous hemorrhage and retinal detachment.

References

Jeon, H., Kim, J., & Kwon, S. OCT angiography of persistent hyaloid artery: a case report. BMC Ophthalmol. 2019 Jul 4;19(1):141.

Gamidov AA, Durzhinskaya MH, Makashova NV, Sakalova ED, Velieva IA. Persistent hyaloid artery in an adult (a case report). Vestn Oftalmol. 2020;136(4):214.
Exploratory and comprehensive description of an Italian cohort of patients affected by leber hereditary optic neuropathy carrying the pathogenic variants m.11778G > A/MT‐ND4 and m.3460G > A/MT‐ND1
Authors: Romagnoli Martina , Carbonelli Michele , Amore Giulia , Fiorini Claudio , Zenesini Corrado , D'Agati Pietro , Tropeano Concetta Valentina , Cascavilla Maria Lucia , Barboni Piero , Caporali Leonardo , Carelli Valerio , La Morgia Chiara
Published: January 2025

Aims/Purpose: This is an observational study to track the disease course of patients affected by Leber Hereditary Optic Neuropathy (LHON), regularly attending the neurophthalmological clinic of the IRCCS ISNB (Bologna).

Methods: To satisfy inclusion criteria, subjects needed a confirmed genetic diagnosis for 2 of the 3 primary LHON mutations (m.11778G > A/MT‐ND4; m.3460G > A/MT‐ND1). There was no restriction on age, and patients could have received idebenone or any other treatment.

Results: 397 subjects from 137 families were enrolled, 196 symptomatic (49%; male: 79%), 201 asymptomatic (51%; male: 40%). Of these, 66 (17%; symptomatic: 55%) carried the m.3460G > A/MT‐ND1 variant, 331 (83%; symptomatic: 48%) the m.11778G > A/MT‐ND4, with a ratio of affected male:female of 2:1 for the first, and 4:1 for the m.11778G > A/MT‐ND4 carriers.

Of the 196 symptomatic patients, 37 had LHON childhood onset and 3 had unilateral LHON.

106 patients (54%) were treated with idebenone and/or lenadogene nolparvovec.

For both mutations the distribution of age at onset is multimodal, and different between males and females. LHON females showed later age at onset (post‐menopausal peak) in the m.11778G > A/MT‐ND4 subgroup, while the m.3460G > A/MT‐ND1 density plot showed a peak in the fertile young age.

Then, visual acuities of both eyes were collected from 1252 outpatient visits. The resulted best‐fitted LOWESS curve depicting the evolution of BCVA over time did not show a difference between m.11778G > A/MT‐ND4 and m.3460G > A/MT‐ND1 symptomatic patients.

Conclusions: We highlight the highest penetrance in females of the m.3460G > A/MT‐ND1 variant, for which females had an age of onset more similar to males at difference with the m.11778G > A/MT‐ND4 for which females had a delayed peak of onset, after menopause. Clinically, the two variants seem to behave similarly. This “real world” study is a precious tool to define genotype/phenotype relationships and highlight the most appropriate subpopulations for clinical trials.
Gut microbial dysbiosis in age‐related macular degeneration
Authors: Vergroesen Joëlle , Vermeulen Jeroen , Thee Eric , Liefers Bart , Klaver Caroline
Published: January 2025

Purpose: The gut microbiome is highly influential in diseases with inflammatory components. Multiple studies showed a link between the gut microbiome and age‐related macular degeneration (AMD). However, no consistent taxa have been reported.

Methods: We included 1372 participants from the Rotterdam Study (RS). AMD features (e.g. [reticular pseudo‐]drusen, retinal pigment epithelium degeneration, and hyperpigmentation) were graded by human graders on color fundus photographs. Next, areas of these features were automatically quantified by a deep learning segmentation model. Stages were determined according to the RS classification (preliminary = 239, early‐intermediate = 75, late = 6). Propensity score matching was performed on age, sex and BMI. Multivariable associations with taxonomic and functional profiles were assessed using zero‐adjusted models (MaAsLin2; Compound Poisson). p‐values were false discovery rate‐adjusted (q‐values). Taxa associated (q < 0.25) with at least two out of seven AMD(‐related) outcomes are reported.

Results: We observed no associations with alpha‐ or beta‐diversity. Nineteen taxa were associated with AMD, of which 7 persisted after additional adjustment for dietary data. Eubacterium xylanophilum group, Lachnoclostridium, Faecalibacterium, Odoribacter splanchnicus and Parabacteroides distasonis were associated with an AMD phenotype. Parabacteroides and Akkermansia were inversely associated with an AMD phenotype. Moreover, 46 MetaCyc pathways were associated with AMD, of which 15 persisted after additional adjustment for dietary data. GLUCARDEG.PWY, PWY.5028, PWY.5347, PWY.5415, PWY.5532, PWY.5971, PWY.6969 and TCA were associated with an AMD phenotype. FOLSYN.PWY, LEU.DEG2.PWY, PANTO.PWY, PANTOSYN.PWY, PWY.6612, PWY0.1586 and PYRIDNUCSYN.PWY were inversely associated with an AMD phenotype.

Conclusions: Several gut microbiota were associated with an AMD phenotype. AMD pathophysiology might be linked to changes in gut‐related metabolic pathways.
ODDB: An interactive database for clinical and translational research in ocular diseases
Authors: Seemab Umair , Kalatanova Anna , Hassan Saad , Tanoli Ziaurrehman , Leinonen Henri
Published: January 2025

Aims/Purpose: To develop and validate a comprehensive web‐based interactive database of ocular diseases, including information of, for instance, associated genes, biomarkers, and medications.

Methods: Initially, a thorough literature review was conducted to identify key ocular diseases and their associated genes and biomarkers. Data was then curated from multiple reputable sources, including peer‐reviewed journals, clinical trial repositories and drug regulatory agency databases. Advanced data integration techniques were employed to link various data types. The database interface was designed to allow intuitive navigation and robust querying capabilities, ensuring ease of access and data utilization. The database underwent internal testing to ensure user friendliness as well as data accuracy and reliability.

Results: The resulting web‐based database encompasses detailed information on a wide array of ocular diseases. The diseases are categorized based on location of primary pathology in various parts of the eye, such as the cornea, retina, and optic nerve, among others. For each disease, the database provides a comprehensive list of biomarkers and associated genes, derived from scientific literature. Additionally, the database includes information of drug regulatory agency‐approved drugs and drugs currently undergoing clinical trials, with detailed descriptions of their therapeutic targets, mechanisms of action and clinical efficacy. The database also features tools for epidemiological analysis.

Conclusions: This user‐friendly database of ocular diseases is a valuable resource for the scientific community, providing a wealth of information that can aid in the advancement of ophthalmology research. By consolidating data of biomarkers, genes, drugs and epidemiology, the database supports basic and clinical research, and facilitates the development of new therapeutic strategies. This initiative sets a precedent for future databases in other medical disciplines.
GPT wars: Creating and detecting fake ophthalmology data sets with artificial intelligence
Authors: Taloni Andrea , Coco Giulia , Pellegrini Marco , Lucisano Andrea , Scalzo Giovanna Carnovale , Scorcia Vincenzo , Giannaccare Giuseppe
Published: January 2025

Aims/Purpose: Recently, our group demonstrated how the Large Language Model GPT‐4 can fabricate fake ophthalmology data sets, designed to support false scientific evidence. The objectives of this study were: (1) to identify peculiar statistical patterns of AI‐generated data sets, (2) to attempt at enhancing the quality of fabricated data for eliminating any discernible mark of non‐authenticity, and (3) to develop a custom GPT trained to detect signs of fabrication.

Methods: Three fictional studies were designed to compare treatment outcomes for a specific ocular disease. First, prompts were submitted to the custom GPT “Data Analyst” to produce 12 “unrefined” fake data sets for the three studies. Then, the custom GPT “Fake Data Creator” was developed to generate 12 “refined” fake data sets, specifically designed to evade authenticity checks. Forensic analysis was performed on all data sets using IBM SPSS. Finally, the custom GPT “Fake Data Detector” (FDD) was developed to replicate the forensic analysis and assign 1 point for each sign of fabrication.

Results: Forensic analysis of the unrefined fake data sets revealed numerous flaws, most notably: name/gender mismatch (n = 12), non‐uniform distribution (n = 11) and repetitive patterns of last digits (n = 7), absence of correlation between study variables (n = 12), and distribution shape anomalies (n = 11). In refined fake data sets, the forensic analysis did not reveal statistical flaws, except for distribution shape anomalies (n = 7). Overall, 5 refined fake data sets (41.7%) passed forensic analysis as authentic. The results of the statistical analyses performed by GPT FDD were identical to those obtained with IBM SPSS, with a mean of 9.67±2.13 (95% IC 8.46‐10.87) and 1.00±1.00 (95% IC 0.43‐1.57) points respectively allocated to unrefined and refined data sets.

Conclusions: Sufficiently sophisticated custom GPTs can perform complex statistical tasks and may be abused to fabricate seemingly authentic ophthalmology data sets, passing forensic analysis.

References

Taloni A, Scorcia V, Giannaccare G. Large Language Model Advanced Data Analysis Abuse to Create a Fake Data Set in Medical Research. JAMA Ophthalmol. 2023; 141(12):1174–1175. doi:10.1001/jamaophthalmol.2023.5162
Localized acute exanthematous pustulosis, a rare reaction on eyelids
Authors: Borghi Luca Manuel Bueno , Simón Cristina Calvo , Remacha Carla Sánchez , Duarte Javier Ramos , Pascual Ana María Abad , González Pablo Tejada , de la Cámara Sahuquillo Edurne , Sánchez Inma Herrero , Fernández Miguel Castillo , Martínez Marta Suñer , Clavería Julia Aramburu , Arias Pablo Cisneros , de Rivas Marta Orejudo , Moscarda Eva Josefina Nuñez , Puyuelo Javier Ascaso
Published: January 2025

Aims/Purpose: The aim of this study is to present a case of localized acute exanthematous pustulosis (ALEP) on the eyelids, a rare adverse cutaneous reaction primarily induced by drugs, with a focus on its clinical features, diagnosis, and management.

Methods: We describe the case of a 21‐year‐old female patient who presented with multiple painful vesicles and pustules on the eyelids, predominantly on the right upper eyelid, with no other body involvement. Initially, she did not report any contact with new cosmetics or other treatments. The initial treatment involved doxycycline and Terramycin. During a second visit, when symptoms worsened, the patient reported that she had used a new cosmetic product. The treatment was modified to topical hydrocortisone, mupirocin, and cefadroxil, and withdrawal of the previous treatment. The patient's progress was monitored.

Results: At the follow‐up visit conducted three weeks later, both the cutaneous lesions and palpebral edema had completely resolved. Mild palpebral hyperpigmentation persisted; however, the symptoms of pruritus and pain had entirely disappeared.

Conclusions: ALEP is a rare, drug‐induced condition that can be effectively managed with proper diagnosis and treatment. This case highlights the importance of having a high suspicion of adverse effects of local treatments and makeup, even when they are not recounted by the patient. Early recognition and intervention are crucial to prevent complications and ensure favorable outcomes.

References

1. Parisi R, Shah H, Navarini AA, Muehleisen B, Ziv M, Shear NH, et al. Acute Generalized Exanthematous Pustulosis: Clinical Features, Differential Diagnosis, and Management. Am J Clin Dermatol [Internet]. 2023 Jul 1 [cited 2024 May 29];24(4):1. Available from: /pmc/articles/PMC10166469/

2. Momin S, Rosso J Del, Michaels B, Cutis NM‐, 2009 U. Acute generalized exanthematous pustulosis: an enigmatic drug‐induced reaction. cutis [Internet]. 2009 [cited 2024 Jun 1]; Available from: https://cdn.mdedge.com/files/s3fs-public/Document/September-2017/083060291.pdf
5XFAD/LC3 mice as a model to investigate autophagy mechanism in the eye
Authors: Ruuth Johanna , Toropainen Elisa , Koskela Ali , Hyttinen Juha , Tanila Heikki , Kaarniranta Kai
Published: January 2025

Purpose: Disturbed proteostasis leads to intracellular protein aggregation and decreased activity of autophagy seen in age‐related macular degeneration (AMD) and Alzheimer's disease (AD). Autophagy is a cellular catabolic recycling process which degrades damaged and aged cellular organelles and protein aggregates. Removed material is sealed by autophagosome which fuses with the lysosome to form an autolysosome. However, autophagy research in vivo is challenging due to lack of specific markers to follow autophagic structures i.e., formation of autophagosomes and autolysosomes. LC3 (microtubule associated protein 1A/1B‐light chain 3) family members are major markers of the autophagosomes located on the autophagosomal membrane. CAG‐RFP‐EGFP‐LC3 (LC3 reporter mice) mice strain enables following the quantity and quality of autophagic structures in the cells. In this study, we investigated the suitability of LC3 reporter mice to study autophagic structures in the 5xFAD mouse eye developing AMD‐like pathogenesis.

Methods: 5xFAD and LC3 reporter mice strains were combined. 5xFAD mice develop AD‐ and AMD‐like pathology and LC3 reporter mice express red fluorescent protein (RFP) and pH sensitive enhanced green fluorescent protein (EGFP) attached to a LC3. Therefore, autophagosomes shows both fluorescence signals (yellow) whereas autolysosomes show only RFP signal. The eyes of 3‐ and 6‐months‐old mice (n = 3‐5) were examined by fluorescence microscopy for autophagic structures.

Results: Fluorescence microscopy revealed that LC3 reporter mice express fluorescent colors especially in the cornea and the retina. 5xFAD/LC3 strain showed accumulation of autophagic structures in the retinal pigment epithelium. Also, the number of autolysosomes were higher suggesting increased autophagy as a response to a cellular damage.

Conclusions: 5xFAD/LC3 reporter mice model seems to be a good model to investigate autophagy mechanism in the eye and degenerative retina processes.
Cryopreservation of corneal endothelial cells in vitro, ex vivo, and on a tissue engineered endothelial graft
Authors: Sagnial Tomy , Coban Melis , Aouimeur Inès , Coulomb Louise , Philippe Gain , He Zhiguo
Published: January 2025

Aims/Purpose: In response to the global shortage of corneas, alternatives such as cell injection therapy and tissue‐engineered endothelial keratoplasty (TEEK) have emerged, both relying on the mass production of primary cultured corneal endothelial cells (CECs). Cryopreservation of corneas (the primary cell culture source), cultured CECs (in vitro), and TEEK grafts (final products) is crucial to facilitate their industrialization and clinical application. While corneal cryopreservation has long been a challenge, advancements in cryoprotectants warrant a renewed investigation. This study aims to assess various cryopreservation methods for CECs n the three different states.

Methods: Ten cryopreservation media and varying cooling rates (‐2°C/min, ‐1°C/min, or ‐0.5°C/min) were first tested on cultured CECs. After thawing, cell survival rates were assessed using Trypan blue staining and an automated cell counter. Subsequently, the best conditions identified for cultured CECs were applied to native CECs adhered to their Descemet's membrane and CECs on TEEKs. Post‐thawing viability was assessed using triple labeling with Hoechst, Ethidium, and Calcein‐AM (Pipparelli et al. IOVS 2011).

Results: A gradual cooling rate of ‐1°C per minute and the cryopreservation medium CryoStor CS10 provided the best conditions for in vitro CECs, ensuring an average viability of 91±1% post‐cryopreservation. However, applying the same conditions to native CECs on corneas or CECs on TEEK grafts resulted in a viability of less than 80%. Upon thawing, CECs tended to detach easily from the DM or bio‐engineered grafts, leading to significant areas without cells.

Conclusions: Cryopreservation is effective for in vitro cultured CECs but remains very challenging for CECs attached to the DM or TEEKs. The next step will be to address cell attachment issues during cryopreservation.

References: Aurélien Pipparelli, Gilles Thuret, David Toubeau, Zhiguo He, Simone Piselli, Sabine Lefèvre, Philippe Gain, Marc Muraine; Pan‐Corneal Endothelial Viability Assessment: Application to Endothelial Grafts Predissected by Eye Banks. Invest. Ophthalmol. Vis. Sci. 2011;52(8):6018‐6025. https://doi.org/10.1167/iovs.10-6641.
Prescribing patterns for preservative‐free glaucoma drops in United Kingdom ophthalmology clinics: A 5‐year multi‐centre study
Authors: Ansari Ejaz , Scott Robert
Published: January 2025

Aims/Purpose: To establish differences in prescribing patterns between various UK glaucoma clinics with respect to preserved (P) versus preservative‐free (PF) drops. To establish the rate of switching between the drop classes and the overall use of PF drops over 5 years.

Methods: This was a multi‐centre cohort study with retrospective case note review (n = 267). The outcome measures included:

Percentage of cases prescribed preserved drops as first‐line treatment,

Percentage of cases switching from preserved to preservative‐free over 5 years,

Percentage of cases switching from preservative‐free to preserved over 5 years,

Average number of switches over 5 years,

Reasons for switching treatment.

A chi‐squared test was used to examine if categorical variables were independent in influencing the test statistics. Statistical significance was determined at the level p = 0.05.

Results: Preserved drops were prescribed first‐line in 72% (192) of cases, of these 48% were switched to preservative‐free drops. Of the 67 (25%) cases where preservative‐free drops were prescribed first‐line by the Hospital Eye Services, 68% were switched to preserved drops by community medical services. The average number of switches over 5 years was 1.7+/‐1.96. This varied from 1.1 to 2.7 switches in each geographical region. The commonest indications for switching from P to PF drops were ocular surface disease, hyperaemia, ocular pain and discomfort. There was no significant difference between centres in the proportion of patients receiving initial treatment with P drops (p = 0.12), but there was a significant difference between centres in switching from P to PF drops (p = 0.01).

Conclusions: Most centres initiated treatment with preserved drops, but 48% of these cases were switched to PF within 5 years due to intolerance of preserved drops. Where PF drops were initiated, the majority were switched to preserved drops by community physicians for unspecified reasons against the recommendations of their glaucoma specialists.
Safety and efficacy of subliminal cyclophotocoagulation in the treatment of glaucoma
Authors: Ramanathan Priyanka , Kaliaperumal Subashini , Behera Geeta
Published: January 2025

Aim: This study was conducted to determine the efficacy of subliminal cyclophotocoagulation in reducing intraocular pressure (IOP) in all subtypes of glaucoma and to study any associated complications of the procedure.

Methods: This was a prospective interventional study conducted on patients with glaucoma on medical therapy requiring > 3 topical medications. Twenty‐seven patients underwent subliminal cyclophotocoagulation with Vitra 810 laser machine (Quantel Medicals, France). The primary outcome measures were IOP control, postoperative complications, and a reduction in the number of antiglaucoma medications (AGM).

Results: 27 eyes were analysed, of which 26 had 6 months follow‐up. Intraocular pressure reduced from 22 mmHg (18,28) at baseline to 16(14,18) at 6 months post‐procedure. The number of anti‐glaucoma medications reduced from 3 (2,3) to 2 (1,3) at 6 months. The reduction in atleast one glaucoma medication was achieved in 61.5% of eyes at 6 months. Most complications, like mydriasis and drop in vision, were transient and self‐limited. Significant complications like vitreous, vitreous hemorrhage and choroidal detachment were seen in 3 patients. The cumulative success rate at 6 months was found to be 84.61%.

Conclusions: Subliminal cyclophotocoagulation is effective in glaucoma patients with IOP control on maximum topical medications. It can reduce the drug burden by at least one medication in the short term.

References

Radhakrishnan S, Wan J, et al. Micropulse Cyclophotocoagulation: A Multicenter Study of Efficacy, Safety, and Factors Associated With Increased Risk of Complications. J Glaucoma. 2020;29:1126–31.

Mohammed F, Jyothi PT, et al. Efficacy and safety of subliminal transscleral cyclophotocoagulation in uncontrolled glaucoma. Indian J Ophthalmol. 2022;70:2911–4.

Tan AM, Aquino MC, Lim ZIL, et al. Micropulse transscleral diode laser cyclophotocoagulation in the treatment of refractory glaucoma. Clin Experiment Ophthalmol. 2010;38:266–72.

Shah P, Bhakta A, Vanner EA, et al. Safety and Efficacy of Diode Laser Transscleral Cyclophotocoagulation in Eyes With Good Visual Acuity. J Glaucoma. 2018;27:874–9.

Chow JY, Wan Norliza WM, Bastion MC. Outcomes of Subliminal Transscleral Cyclophotocoagulation treatment in glaucoma. Med J Malaysia. 2021 Mar;76(2):236‐240.
Molecular responses of the aging retina are sexually divergent in Ephx2−/− mice
Authors: Manicam Caroline , Zare Elahe , Pfeiffer Norbert , Perumal Natarajan
Published: January 2025

Aims/Purpose: Aberrant molecular changes are a major driver of age‐related retinopathies. Furthermore, sexual dimorphism is a key variable in disease predilection, although it is not well defined in preclinical studies. Among the potential targets for mitigating age‐related proteome modifications attributed to vision impairment, we recently unraveled the protective effects of soluble epoxide hydrolase (sEH/ Ephx2) inhibition in glaucoma. Here, we hypothesized that molecular responses of the aging retina are also sexually divergent in the Ephx2‐/‐ (KO) mice.

Methods: Retinae were isolated from 160 young (3‐5 months) and old (12‐24 months) wild type (WT) and KO mice of both sexes. Samples were pooled (n = 5 mice/group/replicate) with 4 biological replicates per group and subjected to robust proteomic and bioinformatic analyses to elucidate the underlying mechanistic changes.

Results: We observed age‐ and sex‐related body weight changes in mice of both sexes, with no significant differences between the WT and KO mice. Proteome profiling showed significant (p < 0.05) differential expression of proteins between the genders, with a significant involvement in the eIF2 and ferroptosis signaling pathways in both sexes. Remarkably, the female sex exhibited striking resilience against ferroptosis, while the male counterpart demonstrated profound activation of this pathway in both WT (p = 4.2×10‐4; z‐score: 1.3) and KO mice (p = 4.2×10‐4; z‐score: 2). Intriguingly, aged WT females were highly susceptible to retinal diseases (p = 9.6×10‐4) and neurodegeneration (p = 9.9×10‐4), but KO significantly regulated proteins related to synaptogenesis (p = 3.8×10‐2) and neurotransmission (p = 1.7×10‐2). In addition, KO significantly activated neuritogenesis (p = 5.4×10‐5) and cell‐cell contact (p = 1.2×10‐3) in both sexes. It is noteworthy that a major upstream transcription regulator, X‐box binding protein 1 (XBP1), which is responsible for maintaining protein homeostasis by ameliorating ER stress, was found only in aged male retinae (WT: p = 3.9×10‐4; KO: p = 8.1×10‐3).

Conclusions: Taken together, we showed for the first time a sex‐related trend in the proteome of aging KO retina, which is crucial for understanding the pathomechanistic underpinnings of age‐related retinal diseases and potential targeted intervention.
Effectiveness of intravitreal antitNF‐ALFA for neuroinflammation control and neuroprotection in experimental rabbit glaucoma model
Authors: Tarlabolen Okyanus Bulut , Baris Mine Esen , Soylu Emrah , Yaman Banu , Kose Timur , Guvenyilmaz Suzan
Published: January 2025

Aims/Purpose: The aim of the study is to create a microbead induced ocular hypertension (OHT) model in rabbits, and to evaluate the effects of intravitreal and intraperitoneal injections of Adalimumab (ADA) on the number of retinal ganglion cells (RGC), retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thickness.

Methods: 15 rabbits of mixed strain (9–12 months old, 3.5‐4kg) were randomized into 4 groups. OHT was induced with microbead injection into the anterior chamber of right eyes. On 7th, 14th days of OHT, ADA was injected at one of two concentrations (2.5mg group 1: G1/5mg group 2:G2) into right eyes of two groups, intraperitoneally 5mg/kg into the third group (G3), and balanced salt solution into fourth group (sham). The left eyes were used as controls. At 40th day, the rabbits were euthanized. Retinal and optic nerve head (ONH) histology was studied with hematoxylin‐eosin and toluidine blue staining.

Results: OHT was induced with microbeads in 13 eyes. 2 rabbits were excluded (endophthalmitis, total hyphema). The average pre‐OHT IOP from all eyes 9.7±09mmHg (8‐11). Statistically significant IOP increase was observed in all subject eyes on day 7 (14±1.4 (12‐18)) (p = 0.01) and maintained until ADA injection (day 21). RGCs in the eyes with elevated IOP were 7.2±1.2 and 7.6±1.5, 6.3+1.1 cells in ADA treated groups, G1, G2, G3, respectively. There was no statistically significant difference between treatment groups. The average RNFL was 125.9±10.9 μm in control, 60.2±9.4 μm in G1, 45.7±2.9 μm in G2, 22.8±2.9 μm in G3, 21.7±10 μm in sham. Significant elevation was observed in G1 compared to all treatment groups. (p = 0.01). The average GCC of control was 45.5±1.9 μm, G1 41.2±2.2 μm, G2 39.3±3.3 μm, G3 34.1±1.6 μm, sham was 38.3±1.1 μm. Significant increase was observed in G1 compared to G3. (p = 0.01).

Conclusions: OHT triggers inflammatory response in which TNF‐α expression is increased around the ONH. Blocking TNF‐α might prevent axonal degeneration and RGC loss by inhibiting this response. These findings may further contribute to the literature for a new treatment strategy for glaucoma using TNF‐α antagonists or inflammation suppressors.
miRNAs from tear fluid‐derived extracellular vescicles to identify patients at high risk of fibrotic lesions after glaucoma surgery
Authors: Sanroque‐Muñoz Marta , Garcia Sergio G. , Clos‐Sansalvador Marta , Font‐Morón Miriam , Botella‐Garcia Jessica , Franquesa Marcella , Loscos‐Arenas Jordi , Borràs Francesc E.
Published: January 2025

Aims/Purpose: Glaucoma is a progressive optic neuropathy characterized by elevated intraocular pressure (IOP). Initial treatment involves topical medication, but surgical intervention is indicated for patients with uncontrolled IOP (1). Yet, post‐surgical tissue fibrosis is a major challenge in 30‐40% of operated patients after 3 years (2). In this work, we investigated the potential of tear fluid‐derived extracellular vesicles (tEVs) from glaucoma‐operated patients to identify specific biomarkers associated with surgery failure secondary to fibrosis.

Methods: Tear samples from 14 healthy controls and 41 glaucoma‐operated patients were collected using the Schrimer's test. Patients were divided into two groups CAGDS1 (one surgical procedure) and CAGDS2 (two surgical procedures due to previous surgical failure). EV‐associated microRNA (miRNA) extraction from tear samples was performed using the Urine Exosome RNA Isolation kit (NORGEN). Total RNA quality was evaluated using an Agilent BioAnalyzer 2100, and miRNA expression was assessed by RNA‐seq using 8 μL of each sample to prepare the libraries.

Results: Bioanalyzer results showed that miRNAs constituted between 70‐95% of the total small RNA content in tEVs, with a miRNA concentration of 2 to 15 ng/μL in all samples. No differences in RNA quality and concentration were detected between them. RNA sequencing was performed loading 500 pM library pools into two independent NEXtSeq‐1000 runs, and 20 million reads of each sample were obtained. Preliminary analysis showed differential expression of several miRNAs between the groups. Fully analyzed results will be presented and discussed.

Conclusions: Tear EV‐derived small RNA extraction is an easy, rapid, and minimally‐invasive method that yields high‐quality miRNA samples starting from a small volume of tears. Similarly to that observed from other sources, RNA sequencing analysis of tEVS could be useful to identify specific glaucoma risk biomarkers, that may help clinicians in their decision making well before therapeutic interventions.
Preoperative fluorometholone in glaucoma surgery: 1 Year clinical and anatomical outcomes with in vivo confocal microscopy (IVCM)
Authors: Tomaselli Davide , Monsellato Gianluca , Calzi Gaia Li , Fantaguzzi Francesca , Lizzio Umberto , Sacchi Matteo , Nucci Paolo
Published: January 2025

Aims/Purpose: To report preliminary data on the preoperative application of topical Fluorometholone in patients requiring glaucoma surgery due to primary open‐angle glaucoma (POAG), evaluating clinical and anatomical outcomes with in vivo confocal microscopy (IVCM) at 1 year follow‐up.

Methods: We conducted a prospective study involving 54 eyes with POAG requiring glaucoma surgery: Trabeculectomy or Minimally Invasive Bleb Surgery (MIBS) (XEN® and PreserFlo®). The sample was randomized: the treatment group (25 eyes) received Fluorometholone 1mg/ml QID for 1 month pre‐surgery, while the control group (29 eyes) did not. IVCM of the conjunctiva was performed at baseline, after 1 month of treatment, and 1 year post‐surgery. Preoperative parameters included goblet cell density (GCD) and dendritic cell density (DCD) as inflammatory markers, while postoperative parameters were density and mean area of intraepithelial cysts (MMD and MMA) as indices of bleb function. Pre and post‐surgery stromal meshwork reflectivity (SMR) served as an indirect marker of stromal collagen.

Results: Preoperative Fluorometholone led to significantly decreased in DCD (p < 0.001) compared to baseline and in DCD (p < 0.001) and SMR (p = 0.014) compared to the control group. At 1 year, there were no significant differences between the two groups in mean IOP, medications, needling procedures, and failure rates. IVCM analysis showed increased MMD in the treatment group compared to the control group (p = 0.028). In the separate analysis, the MIBS treatment subgroup group had lower IOP (p = 0.046) and less medication use (p = 0.032), but this was not observed in the trabeculectomy treatment subgroup. MMD increased in both the MIBS (p = 0.037) and trabeculectomy (p = 0.024) treatment subgroups.

Conclusions: Preoperative Fluorometholone reduced ocular inflammation, improving bleb function at 1 year as detected by IVCM. However, its impact on overall bleb functionality remains unclear, with a clinically detectable improvement only in the MIBS group. Larger studies with longer follow‐up are necessary to fully understand the implications of preoperative Fluorometholone on long‐term surgical outcomes across different types of glaucoma surgeries.
Correlation of biomarkers of oxidative stress and inflammation in tears and aqueous humor of primary open‐angle glaucoma patients
Authors: Sanchez Javier Benitez‐del‐Castillo , Duran Maria Dolores Pinazo , Sáez Sara Mora , Ruiz David Peña , Zanon‐Moreno Vicente , Ramos‐Lopez Juan Francisco , Galarreta‐Mira David
Published: January 2025

Aims/Purpose: Biomarkers improve our knowledge of the risk factors and pathogenic mechanisms of eye disorders. Validation of biomarkers is crucial for addressing an effective translation to the clinical practice. We aimed to find the correlation between oxidative stress (OS) and inflammation (INF) biomarkers obtained from two commonly sampled ocular fluids: tears and aqueous humor.

Methods: A longitudinal, prospective, case‐control study was conducted in 220 participants that were divided into: patients diagnosed of primary open‐angle glaucoma (POAG; n = 115), and patients diagnosed of cataracts, as the comparative group (CG; n = 105). All participants underwent an interview and standardized ophthalmological examination. Reflex tears were collected from the inferior meniscus by capillarity. Aqueous humor was collected at the onset of the programmed glaucoma or cataract surgery. Both samples were stored at ‐80°, until processing to enzyme‐linked immunosorbent assay (ELISA) technique, to determine OS by products (malondialdehyde ‐MDA‐/4 hydroxynonenal ‐4HNE‐/total antioxidant capacity ‐TAC‐) and INF mediators (IL1b, IL6, TNFa, INFg). The R‐core team statistical program was used for data processing.

Results: Mean age was 72 + 9 years in the POAG group and 65 + 10 years in the CG. Gender distribution was homogeneous in both groups of participants. Significantly higher MDA, 4HNE, IL1b, IL6, TNFa, and INFg and lower TAC, were found in tears from the POAG group respect to the CG (p < 0.001). Also, a statistically significant differential profile of OS (MDA, 4HNE, TAC) and INF (IL1b, IL6, TNFa, and INFg ) molecules was detected in the aqueous humor of the POAG patients versus the CG (p < 0.001). Specific significant correlations were found between the above molecules and the imaging data regarding disease stages, as well as, importantly, between the tears and aqueous humor results.

Conclusions: We described a series of OS and INF biomarkers that can provide information of the disease severity. Furthermore, the OS and INF biomarker levels in tears have been shown to correlate with the aqueous humor in POAG patients, but not in the CG. These data enhance the value of non‐invasive tear collection for biomarkers analyses, that may be one useful driver of glaucoma molecular diagnosis and prognosis.
Identification of diagnostic and prognostic biomarkers in dry eye disease in primary open‐angle glaucoma: A cross‐sectional case‐control study
Authors: Sáez Sara Mora , Andrés‐Blasco Irene , Cerdà‐Ibáñez Marta , Peris‐Martínez Cristina , Durán Maria Dolores Pinazo
Published: January 2025

Aims/Purpose: To integrate clinical and molecular data that allow us to identify diagnostic and prognostic biomarkers of dry eye disease (DED) in primary open‐angle glaucoma (POAG).

Methods: A cross‐sectional case‐control study consisting of 182 participants of both sexes, was done. Volunteers were classified into 4 groups: healthy controls (CG; n = 50), DED group (n = 42), POAG group (PG; n = 44), and DED+POAG (n = 46). All participants underwent a complete and systematic medical history, filled out the questionnaires, and were subjected to ophthalmologic examination. Reflex tear samples were collected and subsequently processed using enzyme‐linked immunosorbent assay (ELISA) to quantify the levels of interleukins (IL) ‐1β and ‐18. Statistical analysis was performed with the SPSS 28.0 program.

Results: Mean age of the study participants was 60+15 years, with a total of 56 males (31%) and 126 females (69%). The use of preservative‐containing eye drops was observed in 13% of the POAG patients, and 21% of the DED+POAG group. Clinical data [Schirmer test, tear break‐up time (TBUT), tear meniscus height (TMH) measured by optical coherence tomography (OCT)], and the tear expression of IL‐1β and IL‐18 were significantly different between groups. According to the ocular surface disease index (OSDI) questionnaire, dry eyes were more severe (OSDI = 42) and the IL‐1β and IL‐18 tear levels were significantly higher in 37% of the DED+POAG patients.

Conclusions: We suggest that assessment of TMH, OSDI, and the tear expression of IL‐1β and IL‐18 can be potential biomarkers for identifying patients at risk of DED in the POAG subgroup undergoing treatment with antihypertensive eye drops.
Clinical indicators of inflammation in contact lens wearers despite uncharged tear transforming‐growth factor‐B1 and interleukin 1‐B levels
Authors: Pereira Eduardo Insua , Sampaio Ana Paula , Lira Madalena
Published: January 2025

Aims/Purpose: This study aims to investigate the presence of Transforming Growth Factor (TGF)‐β1 and Interleukin (IL)1‐β in the tears of experienced contact lens wearers; and determine clinical ocular changes induced by the use of these devices.

Methods: Fifty subjects participated in this case‐control clinical trial: Twenty‐five experienced contact lens wearers (31.9± 9.2 years; 4 men) and 25 controls (29.5 ± 7.0 years; 9 men). Tear samples were collected in a single visit during the morning (10 ‐ 12 am). Contact lens wearers were evaluated with the lens in situ. The tear samples were assayed for TGF‐β1 and IL1‐β using Enzyme‐Linked Immunobsorbent Assay (ELISA) kits. Clinical evaluations included blinking frequency; pre‐corneal (NIBUT) and pre‐lens non‐invasive break‐up time (PL‐NIBUT); tear meniscus height; and physiological responses (bulbar, limbal hyperemia, corneal neovascularization) assessment.

Results: Statistical analysis revealed no significant differences in TGF‐β1 (p = 0.337) and IL1‐β (p = 0.114) levels between the groups. However, contact lens wearers exhibited a significantly higher blink frequency (19 ± 10 Vs. Control 16 ± 8 blinks/min., p = 0.036), a lower tear meniscus height (0.22 ± 0.09 mm Vs. Control 0.28 ± 0.07 mm, p = 0.009), and a higher degree of limbal hyperemia (1.4 ± 1.5 Vs. Control 1.2 ± 1.4, p = 0.05). The corneal neovascularization remained similar (0.0 ± 0.2 Vs. Control 0.0 ± 0.1 p = 0.001). PL‐NIBUT was significantly shorter than NIBUT (8.2 ± 6.7 Vs. 13.4 ± 12.1 p < 0.001).

Conclusions: Contact lenses wear induces subtle ocular inflammatory signs, as evidenced by clinical assessments. However, intriguingly, this process does not appear to be mediated by tear‐borne TGF‐β1 and IL1‐β in experienced wearers. The discrepancy suggests alternative inflammatory pathways or compensatory mechanisms might be involved, warranting further investigation.
Post thyroidectomy surprise!
Authors: Agarwal Aakriti , Khan Taskin , Gupta Vishnu , Das Sugourab
Published: January 2025

Aims/Purpose: To report a patient who developed dysthyroid optic neuropathy post thyroidectomy

Methods: Patient who came to the Eye OPD with diminution of vision post thyroidectomy procedure was evaluated

Results: A 57‐year‐old female who had Grave's ophthalmopathy detected 8 months ago, vision 6/6 B/E came to the EYE OPD with sudden exacerbation of symptoms for the past 4 days. She had undergone total thyroidectomy 8 days ago. Her visual acuity was 6/24 both eyes and Color vision was impaired in the both the eyes, left eye more than right eye. On ocular examination there was upper lid retraction both the eyes with scleral show. There was fullness of B/E lower lids with lid lag B/E. EOM were mildly restricted in B/E and pupils were sluggishly reacting B/E, rest anterior segment: WNL. Patient was pharmacologically dilated for fundus examination and both eyes disc pallor was noted.

CECT Orbits was performed which showed significant enlargement and prominence of bilateral extraocular muscles, predominantly inferior and medial rectus (left eye > right). Vertical Barrett's Index of left eye > 60% suggestive of significant optic nerve impingement of left eye. Thyroid tests performed showed profound hypothyroidism with FT4 1.9 pg/ml, TSH: 41 microU/ml.

Euthyroid state was rapidly restored with thyroxine and T3 supplements and optic neuropathy was treated with oral steroids. Patient was kept on regular follow up and dysthyroid optic neuropathy improved significantly with restoration of normal visual acuity.

Conclusions: Dysthyroid optic neuropathy may be precipitated post thyroidectomy in patients developing hypothyroidism suggesting that euthyroid state must be maintained and prompt treatment with steroids of graves ophthalmopathy can restore normal visual acuity.
Evaluation of the retinal vascular and structural changes in migraine patients treated with anti‐CGRP monoclonal antibodies
Authors: Martucci Alessio , Lombardo Marco , Buffon Giacinta , Mercuri Nicola Biagio , Albanese Maria , Durán Maria Dolores Pinazo , Nucci Carlo , Aiello Francesco , Cesareo Massimo
Published: January 2025

Aims/Purpose: Migraine is a disabling and chronic neurological disease characterized by recurrent attacks that can lead to ocular and systemic complications. Several studies have investigated changes in retinal vascular density and structure in migraine patients. This study aims to evaluate vascular and structural changes of the retina in patients with migraine (with and without aura) before and after one‐year treatment with anti‐calcitonin‐gene‐related peptide (CGRP) monoclonal antibodies.

Methods: Ten patients affected by migraine with (MwA) and without aura (MwoA) and ten healthy controls (HCs) were enrolled in this study. Optical coherence tomography angiography (OCT‐A) was performed to assess retinal vessel density and spectral‐domain optical coherence tomography (SD‐OCT) to evaluate foveal thickness, peripapillary retinal nerve fiber layer thickness, and macular ganglion cell layer thickness. In addition, we evaluated these parameters for each group after one year of treatment with anti‐CGRP monoclonal antibodies for MwA and MwoA and one year without treatments for HCs.

Results: At the baseline, MwA patients had significantly lower foveal thickness than MwoA and HCs. From OCT‐A data analysis, we also found that the superficial foveal vascular density values in MwA patients were lower than in MwoA patients and HCs. The foveal avascular zone was significantly enlarged in MwA patients compared to MwoA patients and HCs. After one year of treatment with anti‐CGRP monoclonal antibodies, no statistically significant differences (p‐value < 0.05) were observed in terms of retinal structure and vascularity in all three groups comparing data at the baseline and after one year of treatment.

Conclusions: The results of our study suggest that migraine is associated with vascular and structural retinal changes, especially in patients affected by migraine with aura. The CGRP‐targeted therapy plays an important role in reducing the frequency of migraine attacks and their systemic implications but, nowadays, there is no evidence that this therapy could even have an effective impact on retina vascularity or structure.
Neurophthalomogical assessment in ARSACS syndrome
Authors: Cascavilla Maria Lucia , Battista Marco , Brotto Luigi , Maltecca Francesca , Fantaguzzi Federico , Bianco Lorenzo , Barboni Piero , Bandello Francesco
Published: January 2025

Aims/Purpose: Autosomal recessive spastic ataxia of Charlevoix‐Saguenay (ARSACS) is a neurodegenerative disorder, firstly documented in patients from Quebec, who manifest the early‐onset triad of ataxia, spasticity, and mixed sensorimotor peripheral neuropathy, accompanied by thickening of the retinal nerve fiber layer (RNFL) as observed on optical coherence tomography (OCT).

Methods: To report ten cases of patients with molecularly confirmed ARSACS exhibiting abnormal thinning of the GCL in both eyes. The demographic and OCT analysis were described and discussed. All these patients underwent eye examinations, including best‐corrected visual acuity (BCVA), Ishihara test, Goldmann tonometry and computerized visual field assessment (Humphrey 30‐2, Zeiss). OCT (Triton, Topcon DRI) was used for evaluating RNFL and ganglion cell layer (GCL); a qualitative analysis of perifoveal scans was performed.

Results: The ten patients included were 6 females and 4 males, aged between 30 and 40 years. All patients had a genetically confirmed diagnosis of ARSACS. In ophthalmological assessment, each patient showed a BCVA of 20/20 in both eyes, normal color vision and intraocular pressure. The visual field was unremarkable, except for one patient who exhibited a mild enlargement of the blind spot.

In the OCT scans, all four patients exhibited a certain degree of foveal hypoplasia, with a reduction in the distance measured from the fovea to the optic disc center (FDD). They were also characterized by thickening of the RNFL. Notably, we initially observed a thinning of the ganglion cell layer (GCL) in the temporal sector. However, upon further investigation, we attributed this finding to a systematic error linked to the reduced FDD. Manual re‐centering of the fovea in the OCT scans revealed normal GCL thickness in all examined patients.

Conclusions: Foveal hypoplasia, reduced FDD, and thickening of the RNFL are known characteristics of patients affected by ARSACS, along with optimal BCVA and almost absence of visual field defects.

These findings emphasize the importance of a meticulous image analysis and interpretation in characterize retinal changes in ARSACS patients and highlight the potential impact of imaging technique nuances on diagnostic assessments.