bluuebunny/crossref_metadata_2025 huggingface dataset:
Allogeneic serum eye drops Sjogren syndrome‐related dry eye disease: Clinical evaluation of the ocular surface and in vivo confocal microscopy of the cornea
Authors: Forbice Eliana , Romano Vito , Semeraro Francesco , Pizzolante Teodoro , Passaro Maria Laura , Airaldi Matteo , Ancona Chiara , Bianchetti Andrea
Published: January 2024

Aims/Purpose: To evaluate the symptomatic and clinical efficacy and in vivo confocal microscopy (IVCM) changes of the cornea after allogeneic serum eye drop therapy in patients with Sjögren's syndrome (SS)‐related Dry Eye Disease (DED).

Methods: In this prospective clinical study 15 patients (30 eyes) with primary or secondary SS‐related DED were evaluated for Ocular Surface Disease Index (OSDI) questionnaire, ocular inflammation grade, Schirmer's test, tear film break‐up time (TBUT), corneal and conjunctival staining, and in vivo confocal microscopy (IVCM) analysis.

Results: The average age of patients was 63.87 ± 9.18 years. The patients received treatment for a mean of 81.13 ± 56.84 days. The difference between before and after treatment with allogeneic serum eye drop therapy was statistically significant for OSDI parameters (p = 0.001), ocular inflammation (p = 0.004), TBUT (p = 0.007), Oxford Staining Scale (p = 0.007), Van Bijsterveld score (p = 0.006), basal epithelium density (p = 0.005), intermediate epithelium density (p = 0.041), Corneal Nerve Branch Density (CNBD) (p = 0.040), Beadings density (p = 0.047) and Fibre Tortuosity (p = 0.002).

Conclusions: Allogeneic SEDs treatment in SS related DED patients, showed great results in terms of improvement in dry eye symptoms, clinical signs and IVCM changes. Further studies that aim at propagating and standardizing its production with clear international guidelines are needed.
Comparison between 100% autologous serum and 100% platelet‐rich plasma eye drops and their impact on the treatment efficacy of dry eye in primary Sjogren syndrome
Authors: Wróbel‐Dudzińska Dominika , Przekora‐Kuśmierz Agata , Kazimierczak Paulina , Kosior‐Jarecka Ewa , Ćwikińska‐Haszcz Agnieszka , Żarnowski Tomasz
Published: January 2024

Purpose: The aim of the study was to compare the difference in the composition of 100% autologous serum (AS) and 100% platelet‐rich plasma (PRP) eye drops and assess their impact on the clinical out‐comes after the treatment of severe dry eye (DE) in primary Sjogren Syndrome patients (pSS).

Methods: 22 patients with severe DE in pSS were treated with 100% AS (22 eyes) and 100% PRP (22 eyes) eye drops 5 times per day as monotherapy. The quantification of growth factors (GFs) as fibroblast growth factor (FGF), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), platelet‐derived growth factor (PDGF), nerve growth factor (NGF), transforming growth factor (TGF‐b), insulin‐like growth factor(IGF), fibronectin and substance P in hemoderivates was performed. The main outcomes: Ocular Surface Disease Index (OSDI), Best Corrected Visual Acuity (BCVA), the Schirmer test, tear break‐up time (TBUT), corneal and conjunctival staining according to the Oxford scale, conjunctival hyperaemia and Meibomian gland parameters. The results were compared at the baseline, 1 and 3 months after the treatment. The clinical results were correlated with the concentration of GFs.

Results: Significant differences were observed in the concentration of FGF, EGF, fibronectin, VEGF, PDGF AB, NGF, PDGF, substance P, TGF‐β in PRP compared to AS. There was a statistically significant improvement in BCVA, the Schirmer test, TBUT, Meibomian gland parameters, and the reduction of the OSDI scores, Oxford staining and conjunctiva hyperaemia in each group. There were many correspondences between the level of GFs and the mean change of the clinical outcomes. No adverse events were reported.

Conclusions: Despite the fact that blood derivatives differ in their composition, they seem to be effective, safe in the treatment of severe DE in pSS patients. The signs and symptoms of DE were reduced in both groups. The obtained clinical results and the composition of hemoderivates may indicate the superiority of PRP in relieving the signs and symptoms of DE in pSS patients.
Short‐term effect of rose bengal photodynamic therapy on collagen I, collagen V, nuclear factor kappa B, lysyl oxydase, transforming growth factor beta and interleukin 6 expression of human corneal fibroblasts, in vitro
Authors: Chai Ning , Stachon Tanja , Berger Tim , Li Zhen , Seitz Berthold , Langenbucher Achim , Szentmary Nora
Published: January 2024

Aims/Purpose: To investigate collagen I, collagen V, nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB), lysyl oxidase (LOX), transforming growth factor β (TGF‐β) and interleukin‐6 (IL‐6) expression in healthy human corneal fibroblasts (HCFs) and keratoconus fibroblasts (KC‐HCFs), 24 h after rose bengal photodynamic therapy (RB‐PDT).

Methods: HCFs were isolated from healthy human corneal donors (n = 5) and KC‐HCFs from elective penetrating keratoplasties (n = 5). Both cell cultures underwent RB‐PDT (0.001% rose bengal concentration, 0.17 J/cm2 fluence) and 24 h later collagen I, collagen V, NF‐κB, LOX, TGF‐β and IL‐6 mRNA and protein expression has been determined using qPCR and Western blot, compared to untreated cultures. IL‐6 concentration in the cell culture supernatant has been determined by ELISA.

Results: TGF‐β mRNA expression was significantly lower (p = 0.02) and IL‐6 mRNA expression was significantly higher in HCFs 24 h after treatment (p = 0.01), than in controls. COL1A1, COL5A1 and TGF‐β mRNA expression was significantly lower (p = 0.048; p = 0.02 and p = 0.02) and IL‐6 mRNA expression was significantly higher (p = 0.02) in KC‐HCFs 24 h after RB‐PDT, than in untreated KC‐HCFs. TGF‐β protein expression in HCFs was significantly higher 24 h after treatment, than in controls (p = 0.03). IL‐6 protein concentration in the HCF and KC‐HCF culture supernatant was significantly higher 24 h after treatment, than in controls (p = 0.02; p = 0.03). Nevertheless, collagen I, collagen V protein, NF‐κB and LOX mRNA and protein expression did not differ significantly between any of the RB‐PDT treated and untreated groups.

Conclusions: In conclusion, our study demonstrates that RB‐PDT reduces collagen I, collagen V and TGF‐β mRNA expression, while increasing IL‐6 mRNA and protein expression in KC‐HCFs. In HCFs, RB‐PDT increases TGF‐β and IL‐6 protein level after 24 h. These observations may provide a basis for future research in this field.
PAX6, FABP5 and keratocytes‐characteristic marker expression in human limbal fibroblasts and keratocytes of congenital aniridia and healthy subjects, in vitro
Authors: Li Zhen , Stachon Tanja , Chai Ning , Suiwal Shweta , Fries Fabian , Seitz Berthold , Amini Maryam , Shi Lei , Szentmary Nora
Published: January 2024

Aims/Purpose: To investigate PAX6, FABP5 and keratocyte‐characteristic marker expression in human limbal fibroblasts and keratocytes (LFCs and LKCs) of congenital aniridia (AN) and healthy corneas, in vitro.

Methods: Primary human limbal fibroblasts (LFCs/ AN‐LFCs) were isolated from aniridia (n = 8) and healthy corneas (n = 8) and were cultured in DMEM/F12 with 5% fetal calf serum. Limbal keratocytes (LKCs/ AN‐LKCs) were cultured in low‐glucose serum‐free cell culture medium (LGSF‐medium). Stem cell marker PAX6 and ABCG2, retinoic acid marker FABP5 and keratocyte‐characteristic marker collagen I (COL1A1), collagen III (COL3A1), collagen V (COL5A1), lumican (LUM), keratocan (KER), α‐smooth muscle actin (ACTA2), CD34, aldehyde dehydrogenase 3 family, member A1 (ALDH3A1) expression analysis has been performed by qPCR and Western blot.

Results: PAX6 mRNA expression was significantly lower in AN‐LFCs and AN‐LKCs than in LFCs and LKCs (p = 0.04; p = 0.014). FABP5 mRNA expression was significantly higher in LKC and AN‐LKCs than in LFCs and AN‐LFCs (p = 0.036; p = 0.012) COL5A1 mRNA expression was significantly lower (p = 0.007), KER and ALDH3A1 mRNA expression was significantly higher (p = 0.013; p = 0.007) in AN‐LFCs than in LFCs. COL1A1 and COL5A1 mRNA expression was significantly higher in AN‐LKCs than in LKCs (p = 0.009; p = 0.001). Protein expression did not differ significantly between LFCs/ AN‐LFCs or LKCs/ AN‐LKCs for any of the analysed markers (p ≥ 0.05).

Conclusions: Our study confirmed altered gene expression in aniridia limbal fibroblasts and keratocytes compared to healthy controls. These may play an important role in development and progression of aniridia associated keratopathy.
Correlative microscopy (CLEM) of tarsal conjunctival scraping: A new opportunity in the diagnosis of microbial keratitis
Authors: Troisi Mario , Del Prete Salvatore , Troisi Salvatore , Marasco Daniela , Costagliola Ciro
Published: January 2024

Aims/Purpose: To evaluate the efficacy of correlated Scanning Electron Microscopy (SEM)/Optical Microscopy (OM) analysis of conjunctival scrapings in diagnosing infectious keratitis with prior negative culture tests or ineffective broad‐spectrum antibiotic therapy.

Methods: 102 eyes of 87 patients (45M, 42F) affected by keratitis were evaluated by cytological examination of scrapings of the superior tarsal conjunctiva in OM (Nikon Eclipse 50i) and SEM (JEOL), after 72 h of wash‐out. Inclusion criteria: age > 18 years, corneal epithelial defects from suspected infection, ineffectiveness of previous broad‐spectrum antimicrobial therapy or negative conjunctival swab. Exclusion criteria: ocular surgery <3 months, immunosuppression, allergic keratitis, severe dry eye, ocular herpes, ulcer >3 mm, anterior chamber involvement. Identification of inflammatory infiltrate (OM) and microorganisms (SEM) was performed by two independent operators with the same devices and methodology. Weekly clinical control with new conjunctival scraping for OM and SEM after cycles of therapy were carried out.

Results: Pathogenic microorganisms were detected in 94/102 eyes: Acanthamoeba (22), Candida (18), Mycoplasma (15), Mycobacteria (13), Chlamydia (12), Micrococci (11), Pseudomonas (6), Cocci (6), Aspergillus (5), Fusarium (2); in 14 cases 2 or more different forms coexisted; in 2 cases a subsequent PCR test revealed the presence of HSV‐1; 3 cases showed signs of severe dry eye; other 3 marked eosinophilia. Operator agreement: 99%. The specific treatment for the germs detected determined in all cases clinical and microbiological resolution in 14–49 days (mean 27.6 ± 2.4).

Conclusions: CLEM put in evidence the correlation between phlogistic cells and pathogens, allowing the diagnosis and the treatment of different forms of infectious keratitis and other pathological conditions. The interpretation and repeatability, however, require appropriate training and dedicated equipment.
Segmentation of the fibrillar layer in advanced fuchs endothelial corneal dystrophy: Inter‐oberserver‐reliability and intra‐observer‐repeatability analysis of corneal densitometry images
Authors: Howaldt Antonia , Mestanoglu Mert , Musial Gwen , Jonas Rahul , Cursiefen Claus , Bachmann Björn , Matthaei Mario
Published: January 2024

Aims: Our previous studies state that a central subendothelial collagen‐rich fibrillar layer (FL) is present in about 80% of advanced Fuchs endothelial corneal dystrophy (FECD) corneas which correlates with decreased corneal endothelial cell density and focal oedema formation. In this study, we investigated the previously unknown inter‐observer reliability and intra‐observer reproducibility of FL segmentation on Scheimpflug corneal densitometry images in patients with advanced FECD.

Methods: Preoperative Scheimpflug images of patients receiving DMEK or triple DMEK for advanced FECD were retrospectively analysed. FL‐negative cases were excluded. Images were manually segmented with the open‐source software MITK by two experienced graders. A MATLAB‐based code calculated the region of interest (ROI) area, maximum calliper length, maximum horizontal and vertical dimension, and Dice similarity coefficient for FL‐areas. The intraclass correlation coefficient (ICC) was calculated by IBM SPSS (two‐way mixed, average measures). The FL localization on corneal densitometry were visualized by spatial heatmaps by MATLAB.

Results: Among 308 eyes, 248 were FL‐positive (80.5%) and 60 FL‐negative (19.5%). The average Dice similarity coefficient of FL areas segmented by two graders was calculated at 0.85. Calculations on the segmentations of Grader 1 vs. Grader 2 include: ROI 7.91mm2 ± 4.8 vs. 9.29 mm2 ± 5.0, Calliper length 4.07 mm ± 1.1 vs. 4.21 mm ± 1.0, maximum horizontal dimension 3.85 mm ± 1.1 vs. 3.95 mm ± 1.0, maximum vertical dimension 3.17 mm ± 1.0 vs. 3.3 mm ± 1.0. The ICC was calculated at 0.938 vs. 0.957 vs. 0.930 for ROI (0.955 vs. 0.960 vs. 0.944 calliper length, 0.958 vs. 0.959 vs. 0.946 maximum horizontal dimension, 0.952 vs. 0.941 vs. 0.945 maximum vertical dimension) and 0.85 vs. 0.86 vs. 0.89 for the Dice similarity coefficient (inter‐observer vs. intra‐observer Grader 1 vs. intra‐observer Grader 2). Spatial heatmap analysis demonstrated primarily inferotemporal localization of increased densitometry areas in FL‐positive eyes.

Conclusions: FL segmentation on corneal densitometry images exhibit high inter‐observer reliability and intra‐observer reproducibility scores. We provide evidence for corneal densitometry images as a valid tool to detect FL in advanced FECD and confirm the inferotemporal corneal projection of FL.
Neuroinflammatory findings with corneal COnfocal microscopy in long COVID‐19 patients, 2 years after acute SARS‐CoV‐2 infection
Authors: Suarez Pilar Canadas , Gonzalez‐Vides Leonela , García‐Velasco Marta Alberquilla , Verdejo José Luis Hernández
Published: January 2024

Purpose: To describe corneal confocal microscopy findings in patients with long COVID‐19 with persistent symptoms over 20 months after SARS‐CoV‐2 infection.

Methods: Cross‐sectional comparative transversal study that included a total of 53 patients, 33 patients with Long COVID‐19 and 22 controls matched in age and gender. Long COVID‐19 diagnosis was established according to the World Health Organization criteria Corneal confocal microscopy Heidelberg Retina Tomograph II (Heidelberg Engineering, Heidelberg, Germany) was performed to evaluate sub‐basal nerve plexus morphology (corneal nerve fibre density, nerve fibre length, nerve branch density, nerve fibre total branch density, nerve fibre area, and nerve fibre width). Dendritic cells density and area, along with microneuromas and other morphological changes of the nerve fibres were recorded.

Results: Long COVID‐19 patients presented reduced corneal nerve density and branch density as well as shorter corneal nerves compared to the control group. Additionally, Long COVID‐19 patients showed an increased density of Dendritics Cells with also greater area than that found in the control group of patients without systemic diseases. Microneuromas were detected in 24.2% of Long COVID‐19 patients.

Conclusions: Long COVID‐19 patients exhibited altered corneal nerve parameters and increased DC density over 20 months after acute SARS‐CoV‐2 infection. These findings are consistent with a neuroinflammatory condition hypothesized to be present in patients with long COVID‐19, highlighting the potential role of corneal confocal microscopy as a promising noninvasive technique for the study of patients with long COVID‐19.
“Mucus fishing syndrome”: Presentation of this rare clinical entity along with its therapeutic options
Authors: Mancini Alessandra , Scorcia Vincenzo , Giannaccare Giuseppe
Published: January 2024

Aims/Purpose: The “Mucus fishing syndrome” (MFS) is a rare chronic inflammatory condition involving the ocular surface characterized by the continuous formation, of mucus filaments. The clinical presentation is variable and various underlying ocular surface pathologies including dry eye, blepharitis and allergic conjunctivitis can be associated. Chronic irritation, conjunctival hyperaemia and mucus production are present. On physical examination, patients may present an iatrogenic damage of the conjunctival epithelium due to the mechanical removal of mucus and a vicious circle is usually established which causes further conjunctival irritation and more conspicuous mucous secretion. The treatment involves the elimination of abnormal mucus production and the education of the patient to avoid contact with the ocular surface during the manoeuvres. We present a case of MFS in a young woman affected by meibomian gland dysfunction.

Methods: The diagnosis was reached due to the presence of persistent mucous discharge and the characteristic rose bengal staining pattern. Initial supportive treatment (Tear substitutes and continuous irrigation of the ocular surface) prescribed elsewhere did not provide clear clinical benefits. Therefore, upon presentation a new approach was pursued adding to the ongoing treatment hydrocortisone eye drop 3 times a day, and a mucolytic agent (5% acetylcysteine eye drop) 4 times a day, together with accurate eyelid hygiene (morning and evening). Patient was also informed to avoid mechanical removal of the mucous.

Results: One month after therapy the presence of mucus was reduced and the symptoms improved.

Conclusions: Mucus fishing syndrome is a rare but challenging condition affecting the ocular surface. The objective of the therapy should address the pharmacological lysis of the mucous produced along with the instruction of patient not to compulsively remove the filaments in order to avoid further stress and accelerate healing.
Meibomian gland dysfunction in people who have been in the refuge for a long time during the hostilities in Ukraine
Authors: liudmyla Liudmyla , Bezditko Pavel , Boieva Yuliia
Published: January 2024

Aims/Purpose: To study the indicators of the eye surface in people who have been in the refuge for a long time during the hostilities in Ukraine.

Methods: We recruited 58 patients (main group) aged 32–75 years, who have been in the basement or underground from 3 to 5 month during the hostilities in Ukraine. The control group – 42 patients, aged – 32–72 years, who have been in their houses or flats. Each patients underwent additional examination: the Schirmer's test, the Norn's test, determination of the ocular protection index (OPI), contact meibography (Pult et al., 2012), compression test for evaluation of excretory capacity (Korb, 2005) and quality of the secretion (The International Workshop on Meibomian Gland Dysfunction, 2011) of meibomian gland, and Ocular Surface Disease Index Questionnaire (OSDI). The International Workshop's Classification of Meibomian Gland Dysfunction, 2011 was used to evaluate the severity of MGD.

Results: In 75.8% patients of the main group Schirmer test was 4.8 ± 0.7 mm, Norn test was 4.1 ± 0.8 s, OPI test was 0.54 ± 0.8, test for evaluation of excretory capacity and quality of the secretion of meibomian glands was 2 stage, the mean of OSDI was 56.6 ± 3.4 (p < 0.05). In 71.4% patients of the control group Schirmer test was 14.1 ± 1.6 mm, Norn test was 9.7 ± 0.8 s, OPI test was 0.69 ± 0.1, test for evaluation of excretory capacity and quality of the secretion of meibomian glands was 1 stage, the mean of OSDI was 11.2 ± 1.7 (p < 0.05).

Conclusions: Our findings suggest that 75.8% of all patients who have been in the refuge from 3 to 5 month, have significant changes in the indicators of the eye surface, which corresponds to Meibomian Gland Dysfunction stage 3 and 4 (p < 0.05). 71.4% patients of the control group who have been in their houses or flats have changes in the indicators of the eye surface, which corresponds to Meibomian Gland Dysfunction stage 1 and 2 (p < 0.05). Long stays in the refuge caused significant changes in the surface of the eye, which required treatment for 75.8% of all patients (p < 0.001, respectively).
Corneal topographic indices of Scheimpflug camera in type 2 diabetic and non‐diabetic elderly population
Authors: Yekta AbbasAli , Khabazkhoob Mehdi , Hashemi Hassan , Ostadimoghaddam Hadi , Yekta Reihaneh , Ehsaei Asieh , Yekta Yeganeh , Narooie Foroozan , Siyahkamari Masoud
Published: January 2024

Aims/Purpose: To determine the corneal topographic indices of Scheimpflug camera in type 2 diabetic and non‐diabetic in elderly population of Tehran, Iran.

Methods: A total of 1105 subjects were selected using random cluster sampling from Tehran, Iran and categorized into two groups including diabetics and non‐diabetics. The diabetic group had HbA1c levels ≥6.4% with no other systemic problems. The non‐diabetic participants had normal eye findings and no systemic diseases. The keratometry values, Q‐value, index of surface variance (ISV), index of vertical asymmetry (IVA), central keratoconus index (CKI), keratoconus index (KI), index of height asymmetry (IHA), index of height decentration (IHD), anterior average radius of curvature (ARC), posterior average radius of curvature (PRC), and pachymetric progression index (PPI) values were measured using the Pentacam AXL.

Results: A total participants included 429 diabetic (38.46% male) and 676 non‐diabetic (38.76% male). Only PPIavg and PPImax were higher in the diabetics versus non‐diabetics (p = 0.019 and p = 0.010, respectively). The HbA1c level was 5.47 ± 0.34, 6.70 ± 0.17, and 8.72 ± 1.16 in the first, second, and third group, respectively. There was a significant difference in PPImax between the three groups (p = 0.036). There were significant differences only in IVA, CKI, PPIAvg, and PPImax between different stages of DR (p = 0.045, p = 0.005, p = 0.002, and p = 0.004, respectively). The diabetic subjects were divided into two groups based on the presence of DR. There was a significant difference in ISV, IVA, PPIavg, and PPImax between diabetic subjects with and without DR (p = 0.016, p = 0.022, p < 0.001, and p < 0.001, respectively).

Conclusions: The results of this study showed that DM and DR change several topographic indices and the HbA1c level may affect PPImax. Therefore, special attention should be paid to these patients for different treatment strategies.
Mir‐205‐5p as a regulator agent in cell migration processes
Authors: Sanchez Maria Ybarra , Santos Miriam Martinez , Oltra Maria , Pelluz Javier Sancho , Barcia Jorge
Published: January 2024

Aims/Purpose: Endothelial cell migration is enhanced in pathological processes of the eye involving high glucose, such as diabetic retinopathy (DR). The microRNA miR‐205‐5p is identified as an important regulator of vasculogenesis and could slow down cell migration. The aim of this study is to understand the role of mir‐205‐5p in endothelial cell proliferation under high glucose (HG) conditions.

Methods: HUVEC were seeded at a density of 5.0 × 104 cells/cm2. After 48 h, a wound was produced by scratching cell monolayers with a pipette tip. The cells were treated with different conditioned mediums from ARPE‐19 cells: control media, control media and miR‐205‐5p mimic, HG media and HG media and miR‐205‐5p. Images were taken at 0, 4, 8 and 24 h. The gap distance was analysed with Image J (migration n = 4 and viability n = 6).

Results: HUVEC cells treated with HG media from ARPE‐19 cells close the gap faster than HUVEC cells treated with ARPE‐19 control media or ARPE‐19 control media with mimic miR‐205‐5p. The administration of mimic miR‐205‐5p in HG media significantly reduce migration of HUVEC cells. Besides, the presence of HG for 5 days reduces ARPE‐19 cells viability however miR‐205‐5p mimic protect them, increasing cell viability in control.

Conclusions: Angiogenesis is mostly due to an enhancement of endothelial cell migration. That seems to be related to a reduction of miR‐205‐5p, released from RPE cells. When a miR‐205‐5p mimic was added in the medium, cell migration slowed down.
The miRNA‐mRNA Interactome of human trabecular meshwork cells treated with TGF‐ beta1
Authors: Roodnat Anton , Callaghan Breedge , Doyle Chelsey , Atkinson Sarah , Willoughby Colin
Published: January 2024

Aims/Purpose: Pseudoexfoliation glaucoma (XFG) is an aggressive form of secondary open angle glaucoma, associated with activation of the TGF‐β pathway by TGF‐β1. MicroRNAs are small non‐coding genes that regulate mRNA expression. To investigate the role of TGFβ1 in glaucomatous changes in the trabecular meshwork (TM) and to determine how mRNA expression may be regulated by microRNAs in this condition, we performed a bioinformatics analysis to determine the microRNA‐mRNA interactome.

Methods: Primary human trabecular meshwork cells were obtained from normal donors (n = 4) and treated with TGF‐β1 at 5 ng/mL for 24 h. RNA was extracted and miRNA‐Seq and mRNA‐Seq performed. Differential mRNA and miRNA expression was determined using a bioinformatics pipeline consisting of FastQC, STAR, FeatureCounts, edgeR (miRNA) and DESeq2 (mRNA). Putative interactions between differentially expressed mRNAs and miRNAs, in which the direction of expression of the regulated mRNA was required to be opposite to that of the regulating miRNA, were determined using interaction databases miRTarBase, TarBase, TargetScan and miRWalk. To classify mRNA species by biological function and pathway, gene enrichment was performed using Enrichr.

Results: The resulting microRNA‐mRNA interactome consisted of 1202 interactions. Some highly connected microRNAs were hsa‐let‐7e‐5p, hsa‐miR‐20a‐5p, hsa‐miR‐122‐5p, and hsa‐miR‐29c‐3p. Most genes in all enriched biological functions and pathways were indicated to be regulated by microRNAs. The sub‐interactomes of several specific XFG‐related enrichment terms such as oxidative stress, unfolded protein response, signal molecules and ECM remodelling were determined.

Conclusions: This work presents a genome‐wide microRNA‐mRNA regulatory network for human TM cells treated with TGF‐β1 and may serve to generate unbiased hypotheses about regulatory functions of miRNAs found to be differentially expressed in XFG.
Towards the preclinical diagnosis of diabetic retinopathy and diabetic macular oedema using tear samples
Authors: Ituarte Víctor Alegre , Andrés‐Blasco Irene , Gallego‐Martínez Alex , Casaroli Ricardo , Di Lauro Salvatore , Galarreta‐Mira David , Zanón‐Moreno Vicente , Pinazo‐Duran Maria Dolores
Published: January 2024

Aims/Purpose: A wide spectrum of molecular‐genetic events, including inflammation (INF), angiogenesis (ANG), apoptosis (AP) and the concurrence of miRNAs and target genes, are involved in diabetic retinopathy (DR) and diabetic macular oedema (DMO). To unravel the complex pathogenesis of DR and DMO, we focus on the microvascular endothelial dysfunction (MVED) pathophysiologic pathways.

Methods: Volunteers of both sexes, aged 35–80 years were enrolled and distributed into type 2 diabetics (T2DM), with DR (+DRG; n = 35), without DR (−DRG; n = 35), with DMO (DMOG; n = 28), and controls (CG; n = 40). Sociodemographic and comorbid data, ophthalmologic parameters, and molecular‐genetic variables related to INF, ANG, and AP, assayed in tear samples, were recorded. Statistics were performed by the R Core Team (2022) program.

Results: Most of our participants were middle‐aged (mean age was 58 ± 11 years). Differential expression profile in tears was found statistically significant for SOCS6 gene (involved in INF) target of hsa‐miR‐155‐5p, VEGF‐A gene (implicated in ANG) target of hsa‐miR‐15b‐5p, and the BCL2L2 gene (AP effector) target of hsa‐miR‐10a‐5p, in both the +DRG and DMOG, as compared to the −DRG and CG.

Conclusions: We confirm that INF, ANG, and AP, regulated by the hsa‐miR‐155‐5p, hsa‐miR‐15b‐5p and hsa‐miR‐10a‐5p, and its respective target genes SOCS6, VEGF‐A, and BCL2L2, expressed in tears, are key players in the development of structural and functional chorioretinal changes associated with MVED in DR/DMO patients. We may propose the above insights as potential diagnostic‐prognostic biomarkers for better managing the diabetic eyes and vision.
Genetic landscape of inherited retinal dystrophies in a Welsh Tertiary Referral Centre
Authors: Sanders Francis , Votruba Marcela
Published: January 2024

Aims/Purpose: Inherited retinal dystrophies (IRD) are a group of predominantly monogenic disorders which have genetically heterogeneous origins and display wide clinical phenotypic heterogeneity. The current study aims to describe the clinical diagnoses, demographics, and genetic aetiology of patients in an adult cohort of Welsh patients to provide insight into the rates of genetic diagnosis of IRD. This will help inform patient prognosis and counselling in future clinical encounters.

Methods: A comprehensive database of patients attending the tertiary referral clinic from 2011 to 2022 was compiled contemporaneously. Demographic data were collated from patients' clinical records. Subjects underwent genetic screening, including targeted gene sequencing, next‐generation sequencing‐based gene panel, or whole exome sequencing, to investigate the causative mutations.

Results: A total of 365 probands (191 men and 174 women). The median age at which the patients developed visual symptoms related to IRD was 42 ± 17.7 years (range, 1–86 years). Retinitis pigmentosa (176; 48.2%), Macular Dystrophy (49; 13.4%), and Cone Rod Dystrophy (41; 11.2%) were the most common clinical diagnoses in this cohort. Among all the subjects, a genetic mutation was identified in 193 (52.9%) patients and the genetic aetiology of diseases was confirmed in 147 (40.3%) patients. Pathogenic mutations were identified in 48 retinal genes with the most commonly affected genes being ABCA4, USH2A and GUCY2D with 78, 44 and 13 mutations identified overall.

Conclusions: The establishment of a molecular genetic diagnosis in this group of patients serves as a basis for genetic counselling and will allow patients to enrol in current and future gene‐based clinical trials, and benefit from any future gene‐based treatments.
Needle track technique in strabismus surgery
Authors: Bandhu Seema , Bansal Yashi , Bains Barinder , Moudgil Tania
Published: January 2024

Aims/Purpose: Scleral perforation during the passage of suture needle is a known complication of strabismus surgery.[1–4] The present study was conducted as a pilot study to evolve a safe and easy technique of passing the suture needle through the sclera. A scleral tunnel was created with a 26‐guage needle through which the suture needle was passed.

Methods: After taking clearance from the Institutional Ethics Committee, an interventional study was carried out on twenty consenting patients. A tunnel through approximately half the thickness of the sclera was created with the help of a bent 26‐gauge needle. The suture needle was then passed through this tunnel. Rest of the steps of the surgery were carried out in the conventional manner. In a control group of same number of patients, the surgery was performed in the conventional method. Both the groups were followed up for any complications. Ease of passing suture and surgeons' satisfaction with the technique was noted on a 5‐point Likert scale.

Results: None of the patients in either group suffered from any complications. Four surgeons participated in the study. The average Likert scale score of the surgeons for satisfaction with the technique was 5 on a scale of 5. The score for ease of passage of suture needle was 5 on a score of 5.

Conclusions: The needle track is an easy technique to perform which eases the passage of suture needle through the sclera. This will increase the confidence of Ophthalmologists, specially the residents in performing strabismus surgery.

References

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3. Morris RJ, Rosen PH, Fells P. Incidence of inadvertent globe perforation during strabismus surgery. Br J Ophthalmol. 1990;74:490–3.

4. Olitsky SE, Coats DK. Complications of Strabismus Surgery. Middle East Afr J Ophthalmol. 2015 Jul‐Sep;22(3):271–8. doi: 10.4103/0974‐9233.159692. PMID: 26180463; PMCID: PMC4502168.
Intravitreal bevacizumab in choroidal neovascularisation in Vogt‐Koyanagi‐Harada disease in a child: A review of literature
Authors: Chahir Roukaya , Ghizlane Daghouj , Mtalai Naoual , Elmaaloum Loubna , Allali Bouchra , Elkettani Asmaa
Published: January 2024

Aims/Purpose: Interest of bevacizumab in children in the treatment of choroidal neoplasms in Vogt Koyanagi Harada syndrome.

Methods: In this work we report the case of an extra‐foveal choroidal neovascularization in a child followed for VKH syndrome with a good response to intravitreal injections of bevacizumab.

Results: We report the case of a 12‐year‐old child who initially presented to the hospital in 2020 for bilateral decreased visual acuity and headache. There was no history of systemic disease. Initial visual acuity was 1/10 in both eyes. Biomicroscopic examination revealed granulomatous retrodescemetic precipitates, 2× anterior chamber tyndall, 1× vitreous tyndall, and bilateral exudative retinal detachment associated with bilateral papilledema in both eyes. Based on these findings, a diagnosis of Vogt‐Koyanagi‐Harada syndrome was made, and treatment was initiated with intravenous, oral, and topical corticosteroids. Visual acuity improved to 6/10 OD and 7/10 OS the following month. The patient was then followed up at the university hospital regularly. After controlling the inflammation, steroids were decreased over a period of 2 years but the patient relapsed at high dose to declare cortico‐dependence. Anti‐TNF alpha was started to control the inflammation and visual acuity remained stable until July 2022. Choroidal neovascularization then developed, reducing the patient's visual acuity to 3/10 in both eyes within 1 month. Fluorescein angiography and macular OCT confirmed the diagnosis of extrafoveolar choroidal neovascularization in both eyes. After obtaining informed consent, intravitreal bevacizumab was injected 3 times at 6 week intervals in each eye. After the 6th injection, the patient's best‐corrected visual acuity improved to 8/10 in the right eye and 10/10 in the left eye. The fundus photograph illustrates the regression of the choroidal neovessels. Fluorescein angiography confirmed the reduction in leakage. Choroidal neovascular membranes can cause severe visual impairment and are a major challenge in the management of patients.

Conclusions: This case illustrates that intravitreal bevacizumab has a possible role in the treatment of the disease, with regression of neovascular lesions in the eye.
Ptosis revealing breast carcinoma about a case
Authors: Okomiko Delphes Mathilde Otsasso , Hammoumi Zineb , Houti Sarah , Ghizlane Daghouj , El Maaloum Loubna , Allali Bouchra , El Kettani Asmaa
Published: January 2024

Aims/Purpose: The purpose of our work is to describe the clinical and therapeutic aspects of a clinical case of ptosis revealing breast carcinoma.

Methods: We report the case of a 61‐year‐old patient, with no pathological history, who presented to the ophthalmological emergency department for a unilateral left ptosis, of rapidly progressive onset.

Results: This is a 61‐year‐old patient, with no pathological history, who presents to the ophthalmological emergency department for a unilateral left ptosis of rapidly progressive onset. Ophthalmological examination noted visual acuity at 10/10 in 2 eyes and Parinaud 2 in near vision in 2 eyes, complete ophthalmoplegia of oculomotor nerve (III) with severe ptosis on the left and relative left afferent pupillary deficit. The ophthalmological examination of the right eye was unremarkable. The general examination revealed a right breast mass. Cerebral angio‐MRI revealed four metastatic lesions on the left, above and under tentorial. A mammography showed a diffuse invasive lesion classified ACR 5 (American College of Radiology) on the right. A breast biopsy with histopathological study confirmed the diagnosis of poorly differentiated and invasive lobular carcinoma of the right breast. The patient is currently undergoing chemotherapy treatment.

Conclusions: Acute ptosis is an emergency. Thus, a well‐conducted interrogation as well as a thorough general and ophthalmological examination make it possible to orient the etiological assessment and to take early and adequate management of a pathology that may be life‐threatening for the patient.

References

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2. Audren F. Les paralysies de la IIIe paire crânienne: diagnostic. Pratiques en Ophtalmologie 2011; 5:119 A‐44.

3. Birzu C, Royer‐Perron L, Hoang‐Xuan K. Tumeurs intracrâniennes. La Revue du Praticien 2020; 70(2): 39–46.
Evaluation of machine learning algorithms using OCT and OCT angiography for the diagnosis of multiple sclerosis
Authors: Lozano María Pilar Rojas , Mesa Pablo García , Gutiérrez Nuria Díaz , Valverde Juan José Gómez
Published: January 2024

Aims/Purpose: We present a comprehensive evaluation of machine learning (ML) algorithms using Optical coherence tomography (OCT) and optical coherence tomography angiography (OCT‐A) for the diagnosis of Multiple sclerosis (MS).

Methods: Prospective observational study using OCT volumes acquired with Cirrus HD‐OCT 5000 (Carl Zeiss, Meditec, Dublin, CA, EEUU) using the scanning protocols Optic Disc Cube 200 × 200 and Macular Cube 512 × 128, and OCT‐A macular volumes 175 × 350 with FOV 6 × 6 mm and OCT‐A of the Optic Nerve Head (ONH) with FOV 4.5 × 4.5 mm. The total data set consisted of 79 eyes of 40 patients with MS and 54 eyes of 27 control subjects. We evaluated classification algorithms such as Support Vector Machines, k‐Nearest Neighbour, Decision Trees, Random Forest, Extra Trees Classifier and Gaussian NB using data extracted from Ganglion Cell Analysis (8 parameters), Macular Thickness Analysis (7 parameters) and Optic Disc Analysis (5 parameters) from the OCT volumes and 5 parameters from the analysis of the macular OCT‐A volumes and 6 parameters from the analysis of the ONH. We studied all the ML algorithms considering three scenarios: OCT (20 parameters), OCT‐A (11 parameters), and OCT + OCT‐A (31 parameters). The models were trained using a 5‐fold cross‐validation strategy. We calculated the accuracy, F1‐score for each model and the area under the curve (AUC) was used to select the best ML algorithm. We applied SHAP (SHapley Additive exPlanations) to explain the output of the best ML model.

Results: For the MS diagnosis, the best results were obtained for OCT with Gaussian NB (accuracy 0.865 ± 0.085, F1‐score 0.864 ± 0.086 and AUC 0.871 ± 0.081), for OCT‐A with Random Forest (accuracy 0.832 ± 0.032, F1‐score 0.832 ± 0.043 and AUC 0.831 ± 0.043) and for OCT + OCT‐A with Gaussian NB (accuracy 0.885 ± 0.028, F1‐score 0.886 ± 0.028 and AUC 0.891 ± 0.034). The input parameters with the highest contribution to the model's predictions were the minimum ganglion cell thickness and the temporal flow index in the ETDRS grid.

Conclusions: This study highlights the efficacy of machine learning techniques in utilizing combined parameters from OCT and OCT‐A images of the macula and ONH tests to facilitate early diagnosis of MS. Moreover, it underscores the significance of ophthalmic examination in the comprehensive management of the disease.
Ocular tics in Paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS)
Authors: Dore Stefano , Zinellu Angelo , Satta Daniele , Boscia Giacomo , Murgia Carlo , Pinna Antonio
Published: January 2024

Aims/Purpose: Little is known about ocular tics in Paediatric Autoimmune Neuropsychiatric Disorders associated with Streptococcal infections (PANDAS). The purpose of this retrospective study was to assess ocular symptoms in 40 children with PANDAS.

Methods: The clinical records of children with PANDAS referred to the Ophthalmology Unit, Azienda Ospedaliero‐Universitaria di Sassari, Sassari, Italy, between 2010 and 2019 were examined. The detection of ocular tics was investigated. Data about plasma antistreptolysin O (ASO) and anti‐DNAse b titres, erythrocyte sedimentation rate (ESR), plasma C‐reactive protein (CRP), and antibiotic use were recorded and statistically analysed.

Results: 40 children (34 boys, 6 girls; mean age: 7.6 ± 2.5 years) with PANDAS were identified; 33 (82.5%) showed ocular tics, whereas the remaining 7 (17.5%) had extraocular tics. Children with ocular tics had significantly higher plasma values of anti‐DNAse b antibodies (p = 0.04) and CRP (p = 0.016) than those with extraocular tics. A course of oral antibiotics was given to 25 (76%) out of 33 children with ocular tics. All the treated patients showed marked improvement/complete resolution of symptoms; conversely, no improvement was observed in those untreated. A post‐antibiotic recurrence occurred in 8 (32%) children.

Conclusions: Results suggest that higher plasma values of anti‐DNAse b antibodies and CRP may play a role in the pathophysiological mechanisms underlying ocular tics in PANDAS. Oral antibiotics may be beneficial in improving ocular symptoms. Further research is necessary to confirm our findings.
Changes in the structure and function of the visual pathway in subjects at high risk for the development of Alzheimer's disease: 27 months of follow‐up
Authors: López‐Cuenca Inés , Sanchez‐Puebla Lidia , Gutierrez María Álvarez , Salobrar‐Garcia Elena , Elvira‐Hurtado Lorena , Barabash Ana , Ramirez‐Toraño Federico , Fernández‐Albarral José A. , Matamoros José A. , Salazar Juan Jose , Ramirez Jose Manuel , de Hoz Rosa
Published: January 2024

Aims/Purpose: In addition to advanced age, two of the most important risk factors for the development of Alzheimer's disease are having a family history of the disease (FH+) and being a carrier of at least one Ɛ4+ allele for the ApoE gene (ApoE Ɛ4+). AD generates changes in the retina and visual function when the disease is established, so the aim of the present work is to know if these changes appear in healthy subjects but with high genetic risk to develop the disease and to analyse if these changes evolve along 27 months of follow‐up.

Methods: A retinal thickness analysis by optical coherence tomography and visual function by assessing visual acuity (VA), contrast sensitivity (CS), colour perception, perception digital test and visual field analysis was completed by all participants. For structural findings analysis subjects were divided into (FH+ ApoE Ɛ4+) and (FH‐ ApoE Ɛ4‐) groups and for functional analysis these subgroups were subdivided by ages between 40 and 60 years and subjects over 60 years.

Results: After 27 months of follow‐up, the FH+ ApoE Ɛ4+ group experienced changes in the thickness of all retinal layers except the outer layers. In this group, the inner nuclear layer showed progressing changes, but there was no progression in visual function. However, compared to the FH‐ ApoE Ɛ4‐ group at 27 months, the improvement in visual acuity and contrast sensitivity (3 and 12 cpd) observed during the initial visit was maintained.

Conclusions: In cognitively healthy individuals at high risk of developing AD structural changes in the retina continue to progress after 27 months, while functional changes detected at the beginning remain stable.
Retrobulbar haemorrhage and globe perforation after botulinum toxin injection into the medial rectus
Authors: Artola Ines , Antón Maria Teresa Cedazo , Sanchez Manuel Morales , Pernas Sergio , Hernandez Eduardo Conesa , Carretero Manuel Moriche
Published: January 2024

Aims/Purpose: The aim of this communication is to show a recent case of both retrobulbar haemorrhage (RH) and probable globe perforation (GP) after botulinum toxin (BT) injection in the medial rectus of the right eye.

Methods: We selected a recent case seen at our hospital. A 5u BT injection was performed under topical anaesthesia and guiding electromiography into the medial rectus due to a VI cranial nerve palsy. 2 min later the patient claimed intense pain and we evidenced a sudden growing periocular oedema and progressing exophthalmos. Retrobulbar haemorrhage was diagnosed and immediate canthotomy and cantholisys were performed, with consequent haemorrhage drainage. In the 24 h follow‐up visit, our patient claimed blurry vision and floaters. VA RE was 0.3 (before BT 0.7). Important corneal oedema and 3–4 + tyndall was observed. In the funduscopic exploration severe hemovitreous was observed; and an ocular ecography was performed, which showed no signs of retinal disruption. As vitreous started clearing and VA and floaters improved, observational treatment was decided. When we became able to see the retina with detail a possible perforation hole was seen in the infero‐medial quadrant, with no signs of traction or retinal elevation.

Results: 3 months later, VA was 0.8 e° 1. Funduscopy showed an applied retina, with only a few persistent fibrine remainders in the inferior quadrant. Good‐coloured optic disc, with physiologic excavation and no signs of atrophy.

Conclusions: Eventhough RH and GP are quite rare complications after BT infection, we should always take them into consideration. We also wanted to highlight these complications treatment.

RH: Immediate canthotomy and cantholysis must be performed

GP: close observation must be followed in order not to miss a retinal detachment.

Plus, to avoid them we should be careful to perform the right technique and to use the electromiograph to guide us into the muscle.
Optic nerve disorders and reduced visual acuity in children. Differential diagnosis
Authors: Díaz‐Barreda Mª. Dolores , Boned‐Murillo Ana , Fernández‐Espinosa Guisela , Sopeña María , Álvarez Marta Arias , Pinilla Isabel
Published: January 2024

Aims/Purpose: Low visual acuity (VA) in children requires meticulous investigation in search of possible organic causes. Once an alteration in the optic nerve (ON) has been detected, differential diagnosis is essential due to the different prognosis and management of each entity.

Methods: We report the case of a 10‐year‐old black girl who went to the ophthalmologist for decreased VA in the left eye (LE) with no other history, signs or symptoms. On examination she had VA in the right eye (RE) 1 (Snellen decimal scale) and 0.1 LE. No torticollis or stereopsis, exotropia and convergence deficit in the LE. Normal fundus of eye (FE) RE; LE papilla larger and pale, centred staphylomatous excavation with central whitish area, vessels emanating from the periphery of the ON and alteration of the surrounding pigmentation, peripheral retina hypopigmented. Optical coherence tomography (OCT) of macula was normal; of the ON was very altered. Ultrasound showed protrusion of the LE “bottleneck” disc.

Results: In view of the suspicion of Morning Glory Syndrome (MGS), magnetic resonance imaging (MRI) and angio‐MRI were requested to rule out alterations in the central nervous system (CNS), especially vascular malformations. After explaining the findings and poor visual prognosis we opted for occlusions in the RE, improving VA to 0.2 OI. We consulted paediatrics, genetic testing and close follow‐up, paying special attention to the retina due to the association with choroidal neovascularisation (CNV) and retinal detachment (RD).

Conclusions: The characteristics of MGS can be confused with other pathologies, especially ON coloboma. Peripapillary staphyloma, ON dysplasia or aplasia, advanced glaucoma, Aicardi's disease and Papillorenal disease must be ruled out. Once diagnosed, possible systemic associations must be studied due to their potential severity and follow‐up is essential, as a high percentage will present ophthalmological complications.