bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel pathomechanisms of impairment of native tear protein complexes in aqueous deficient dry eye syndrome
Authors: Perumal Natarajan , Hering Janine , Pfeiffer Norbert , Grus Franz , Manicam Caroline
Published: January 2024

Aims/Purpose: Dry eye syndrome (DES) is a common yet deplorable disease of the ocular surface with high global prevalence. The pathomechanisms underlying the impairment of the native tear protein complexes remain unexplored. This study established a quantitative proteomics approach to characterize the novel protein complexes and unravel their functional roles in tears of DES patients.

Methods: Tear samples were collected using Schirmer's strips from aqueous‐deficient DES (DRY, n = 16) and healthy (CTRL, n = 16) subjects following comprehensive DES clinical examinations. The native tear protein complex profiles were elucidated employing a customized blue native gel electrophoretic (BN‐PAGE) combined with mass spectrometry (MS)‐based proteomics strategy. In‐silico bioinformatics tools were employed for gene annotation analysis of the complexes.

Results: Five major native protein complexes designated as complex I (cI, 800 kDa), II (cII, 400 kDa), III (cIII, 240 kDa), IV (cIV, 140 kDa) and V (cV, 66 kDa) were characterized for the first time in human tears. Interestingly, a cluster of immune‐related proteins identified in cI (e.g., IGHA1) were annotated to complement pathways and was found to be significantly increased in abundance in DRY vs. CTRL (p = 8.2 × 10−3). Likewise, increased abundance of another cluster of proteins annotated to inflammatory response (e.g. S100A9) in DRY (p = 1.7 × 10−2) was associated to cIII. On the contrary, cII was largely composed of lacrimal‐specific proteins (e.g., LYZ), which was found to be decreased in abundance in DRY (p = 2.4 × 10−2). Similarly, decrement of antimicrobial proteins in cIV (e.g., LACRT) was observed in DRY (p = 1.7 × 10−2). The expression of a cluster of carrier proteins involved in protein–protein interactions (e.g., ALB) was annotated in cV, which was increased in DRY (p = 4.4 × 10−3). Noteworthy, 35 new DES markers were identified with this methodological approach.

Conclusions: Collectively, a tear‐customized BN‐PAGE‐MS analysis was instrumental to decipher the multifaceted biological functions of novel native protein complexes in human tears. For the first time, the intricate molecular mechanistic changes underlying these protein complexes in DES were unravelled, which could be instrumental for potential development of therapeutic strategies in ameliorating DES.
Corneal laceration with expulsive iridodialysis and vitreous prolapse following blunt trauma
Authors: Arun Kirupakaran , Danboyi Bitrus
Published: January 2024

Aims/Purpose: A full‐thickness corneal laceration can occur following blunt trauma and is an ocular emergency that requires decisive immediate, short and long‐term management. We describe an unusual case of blunt trauma leading to dehiscence of an old cataract wound with traumatic expulsive Iridodialysis associated with vitreous prolapse to create awareness among ophthalmologists on key diagnostic features and patient specific management for this condition.

Methods: An 84 year old female presented to the eye emergency department following accidental trauma to her right eye. Ocular examination revealed a 3 mm corneal laceration that was just away from the limbus which was compatible with the incision used for prior cataract surgery over 10 years prior. There was signs of expulsive Iridodialysis as well as vitreous prolapse from this wound with associated ruptured posterior capsule, inferior IOL subluxation and pupil block angle closure.

Results: Immediate management included excision of prolapsed vitreous and iris from the corneal laceration, placement of bandage contact lens and an eyeshield, as well as topical and systemic antibiotic therapy, topical steroids and IOP control. Within 3 days, the corneal laceration remained sealed following removal of the bandage contact lens and surgery was performed which included pars plana vitrectomy, IOL repositioning and corneal suturing.

Conclusions: We report this case to emphasize the importance of careful anterior segment examination in cases of suspected globe rupture to identify the site of the opening and to always consider old surgical wounds. Once confirmed, no pressure should be placed on the eye to reduce the risk of further extravasation of intraocular contents.
Prevalence of tomographic features associated with subclinical oedema in Fuchs dystrophy across three commercially available corneal tomographers
Authors: Passaro Maria Laura , Ancona Chiara , Airaldi Matteo , cucco rosangela , Semeraro Francesco , Costagliola Ciro , Romano Vito
Published: January 2024

Aims/Purpose: Specific tomographic alterations suggestive for subclinical oedema have a known impact on FED prognosis. Here, we compare the prevalence of tomographic alterations associated with subclinical oedema in patients affected by Fuchs Endothelial Dystrophy (FED) imaged with corneal tomographers employing three different technologies.

Methods: Patients with a clinical diagnosis of FED referred to the cornea service underwent tomography with 3 different devices: the Pentacam Scheimpflung camera (Oculus, Germany), the Casia2 AS‐OCT (Tomey, Japan), and the Precisio 2 blue‐light slit‐scanning tomographer (IVIS, Italy). All patients had confirmed corneal guttae at slit‐lamp examination. Subjects were classified into FED with no oedema, FED with subclinical oedema, and FED with clinical oedema according to a validated classification based on pachymetric and posterior elevation maps appearance on the Scheimpflung camera. The prevalence of these features was compared across the 3 devices, then two experienced ophthalmologists (M.A., M.L.P.) assigned a 0–3 score according to their evidence. A mixed‐effects binomial model estimated Odds Ratios (OR) for the scores of the 3 devices.

Results: A total of 30 eyes were included: 7 eyes presented with clinically defined oedema, 18 eyes with no clinical oedema but tomographic features suggestive of subclinical oedema, and 5 eyes with no oedema and no tomographic alterations. The prevalence of Loss of parallel isopachs, Displacement of thinnest point, and Focal posterior depression did not differ between devices. However, identification of Loss of parallel isopachs was most evident on Precisio 2 compared to Pentacam (OR 9.6, p = 0.007), and the Displacement of thinnest point was most evident on Precisio 2 compared to both Pentacam and Casia2 (OR 6.9, p = 0.01 and OR 15.1, p = 0.005). 3 eyes showed alterations only on Precisio 2, one of which was later scheduled for DMEK.

Conclusions: Scheimpflung camera, AS‐OCT, and blue‐light slit‐scanning based tomographers were all able to detect tomographic changes in FED. Nevertheless, our results suggest that the blue laser, slit‐scanning tomographer might be able to detect earlier, and delineate better, subclinical changes in FED.
Evaluation of drug release, mucoadhesive and viscoelastic performances of Netildex gel versus an antibiotic‐steroid combination system
Authors: Pepe Veronica , Cuffari Francesco , Curatolo Maria Cristina , Abbate Ilenia
Published: January 2024

Purpose: The poor bioavailability and therapeutic response exhibited by conventional antibiotic‐steroid ophthalmic solutions due to rapid precorneal elimination of the drug may be overcome using a gel systems. Netildex gel is a preservative‐free product based on netilmicin and dexamethasone indicated for the treatment of inflammatory ocular conditions of the anterior segment and ocular adnexa including post‐cataract surgery. The current investigation evaluated the in vitro drug release, viscosity and mucoadhesion profile of Netildex gel in comparison to a gel matrix with regard to steroid and antibiotic delivery.

Methods: In vitro drug release was assessed using Franz‐type diffusion cells, under sink condition, exploiting a simulated tear solution (STS) as dissolution medium and a regenerated cellulose membrane. Evaluation of mucoadhesive and viscoelastic properties were performed by texture analyzer TA‐XT2 and rheometer.

Results: The dexamethasone and netilmicin release curves in Netildex gel exhibited a better sustained and controlled pattern over an extended time period (48 h) with respect to another gel system containing anti‐inflammatory and antibiotic drugs. The results were expressed as cumulative percentage of drug release and the antibiotics‐release kinetics from the polymeric matrix, evaluated by different mathematical models. The determination of detachment force demonstrated a significant mucoadhesive strength of Netildex gel compared to mucin. Moreover, rheological analysis of Netildex gel highlighted a strong pseudo‐plastic behaviour under shear strain due to its formulation features.

Conclusions: Overall, Netildex gel exhibits a sustained and controlled drug release of both dexamethasone and netilmicin from polymeric matrix thanks to its viscoelastic and mucoadhesive properties allowing to prolong drug residence time on the ocular surface. These data support the reduced administration frequency while maintaining the same efficacy and simultaneously favouring patients' compliance [1].

Reference

1. Mencucci R. et al. Adv Ther (2022) 39: 5474–5486.
Bowman's layer transplantation—A new hope for regaining of correct ocular surface
Authors: Wyroslak‐Bednarek Diana , Jurowski Piotr
Published: January 2024

Aims/Purpose: To present a novel surgical technique of selective Bowman's layer transplantation as well as results of the surgery in patients with neurotrophic corneal ulcers.

Methods: 3 eyes from 3 patients with neurotrophic corneal ulcers who underwent corneal grafting with Bowman's layer. Pre‐ and postoperative analyses of the anterior segment of the eye were based on optical coherence tomography and slit lamp assessment.

Results: Postoperatively a gradual corneal stroma restoration and fast corneal epithelialisation were noticed.

Conclusions: Based on our observations, stiff and firm structure of Bowman's layer is supposed to strengthen corneal surface and maintain its shape. It acts also as an anti‐pathogen and anti‐toxin corneal barrier. Application of this acellular corneal layer transplantation to cover trophic corneal ulcers is an interesting, modern and crucial method of neurotrophic keratitis treatment.

Reference

1. Hsu HY, Modi D. Etiologies, quantitative hypoesthesia, and clinical outcomes of neurotrophic keratopathy. Eye Contact Lens 2015;41(5):314–7.

2. Sacchetti M, Lambiase A. Diagnosis and management of neurotrophic keratitis. Clin Ophthalmol 2014;8:571–9.

3. Mantelli F, Mauris J, Argüeso P. The ocular surface epithelial barrier and other mechanisms of mucosal protection: from allergy to infectious diseases. Curr Opin Allergy Clin Immunol. 2013 Oct;13(5): 563–8.

4. Wilson SE. Bowman's layer in the cornea‐ structure and function and regeneration. Exp Eye Res 2020 Jun;195:108033.

5. Lagali N, Germundsson J, Fagerholm P. The Role of Bowman's Layer in Corneal Regeneration after Phototherapeutic Keratectomy: A Prospective Study Using In Vivo Confocal Microscopy. Invest Ophthalmol Vis Sc. 2009 Sep;50(9):4192–8.
Contribution of TRPM8‐mediated activity to thermally‐evoked reflex blink
Authors: Diaz‐Tahoces Ariadna , Aleixandre‐Carrera Fernando , Velasco Enrique , del Carmen Acosta Maria , Gallar Juana
Published: January 2024

Purpose: To study the characteristics of reflex blink evoked by cold and heat stimulation of the ocular surface (OS), and to define the contribution of TRPM8 to the process.

Methods: The orbicularis oculi muscle electromyography signal (OOemg) and the ocular surface temperature (OST; measured with a small thermoprobe placed on the cornea) were recorded in anaesthetised rats. OS temperature changes (ΔT) were induced by topical instillation of 20 μL drops of saline solution at different temperatures (15–50°C). ΔT and the area under the curve (AUC) and duration of the evoked OOemg signals were analysed before (control) and after topical treatment with the TRPM8 antagonist N‐(3‐aminopropyl)‐2‐[(3‐methylphenyl) methoxy] ‐N‐(2‐thienylmethyl) benzamide hydrochloride (AMTB; 1 mM).

Results: Mild (−ΔT 0.1–5°C) and intense (−ΔT 5–15°C) cooling always evoked a reflex OOemg signal (probability = 1). AMTB significantly reduced the probability of cooling to evoke blink (probability = 0.26 and 0.57 for mild and intense cold stimuli, respectively; p < 0.001). OOemg AUC and duration were also significantly reduced by AMTB (p < 0.01). Probability of evoking OOemg signal by mild (ΔT 0.1–5°C) and intense (ΔT 5–15°C) OS heating was low (0.30 and 0.59 respectively), and their duration and AUC were significantly smaller than those evoked by cooling (p < 0.001). Although AMTB did not modify the probability of heating stimuli to evoke OOemg signals (0.17 and 0.57 for mild and intense heating, respectively), the duration of signals evoked by mild heating stimuli was significantly increased (p < 0.001).

Conclusions: Cold stimuli applied to the ocular surface always evoked reflex EMG activity of the lid muscle. This ability of cooling stimuli to evoke reflex blink is mediated by TRPM8 channels, whose pharmacological blockade reduces both the probability to evoke the reflex blink and its amplitude.

Support: PID2020‐115934RB‐I00 from DOI: MCIN/AEI/10.13039/50110001103; CIPROM/2021/48 from Generalitat Valenciana, Spain.
Repeatability of ANTERION in subjects with keratoconus
Authors: Larraz Marta Sancho , Blasco‐Martinez Alejandro
Published: January 2024

Aims/Purpose: The aim of this study was to study the repeatability of ANTERION in subjects diagnosed with keratoconus.

Methods: The subjects selected had a previous diagnosis of keratoconus. These subjects were divided into three groups, according to the keratoconus treatment: subjects without treatment, intrastromal ring implantation and crosslinking. Subjects with pathologies with ophthalmological repercussion or previous surgeries were excluded.

Three measures were performed with ANTERION in patients with keratoconus to evaluate the repeatability. These exams were performed with Cataract and Metricts module; therefore, six measurements were performed per patient and eye.

Results: The parameters that showed values of coefficient of variation (CV) >5% in all the evaluated groups were: the vertical coma value, the difference between the thickness of the inferior–superior stroma and the eccentricity of the anterior and posterior corneal surface. In the groups with intrastromal ring segments and crosslinking, a CV >5% was obtained in the measurements of the minimum epithelial thickness and in the difference between the inferior–superior epithelial thickness. In the crosslinking and untreated groups, a CV >5% was obtained in the horizontal coma value. In the groups with intrastromal ring segments and without treatment, a CV >5% was obtained in the corneal RMS value and in the Score, which gives a value of the degree of keratoconus.

The subjects implanted with intrastromal rings segments, a CV >5% was obtained in the measurements of the epithelial thickness at the point of greatest thickness.

Conclusions: A parameter was considered to show low repeatability when its CV was >5%. The topographic measurements of K corneal and elevation values show good repeatability in subjects diagnosed with keratoconus. However, ANTERION shows a low repeatability in aberrometric values, and in measurements related to the stage and progression of the keratokonus.
May a post‐radiation ocular surface disorder compromise penetrating keratoplasty surgery? A case report
Authors: Gjukaj Driton , Todorova Margarita
Published: January 2024

Aims/Purpose: Ocular surface disorder after ocular radiation therapy, even commonly reported, remains overlooked. Any delay in diagnosis may lead to vision threatening complications. The presented case highlights the clinical outcome of a severe post‐radiation ocular surface disorder, the importance of intense therapy and the limitations of further surgical interventions.

Methods: Case report.

Results: A 34‐year‐old woman was referred with complains of painful and reddish right eye since years. Her medical history revealed an iris melanoma excision at the age of 29 years. Due to recurrence, a proton beam treatment has been performed thereafter. Consequently, the patient developed post‐radiation retinopathy with macula edema, secondary glaucoma, cataract, as well as a severe ocular surface disorder with corneal decompensation and band keratopathy. Several surgical treatments have been attempted among which: phacoemulsification with IOL implantation, trabeculectomy with mitomycin C. Due to refractory glaucoma a Baerveldt glaucoma drainage was necessitated, thereafter. Despite these various therapeutic approaches, there was no improvement of the ocular surface problem. With increasing deterioration of the corneal situation, a penetrating keratoplasty, has been discussed.

Conclusions: The continuous worsening of clinical symptomatology of the proton beam radiotherapy ocular surface disorder can be the result of a post‐radiation syndrome. An ischaemic retinopathy and anterior segment disorder lead to engorgement of posterior and anterior segment tissues. Gradual expansion of ischemia, vasculitis and inflammatory mediators compresses the retinal tissue leading to recurrent macular oedema; as well as to secondary glaucoma and corneal decompensation. Due to the worsening of the clinical presentation of ocular surface disorder a penetrated keratoplastic surgery has been discussed. It remains however still questionable whether such patients would make profit from penetrated keratoplastic surgery, as the resulting corneal stromal lymphangiogenesis and hemangiogenesis, in the presence of post‐radiation keratopathy, are essential conditions for allograft rejection.
New non‐toxic fluorescent marker for quantifying the viability of corneal endothelial cells
Authors: Maurin Corantin , Mentek Marielle , Vaitinadapoule Hanielle , Ulrich Gilles , De Nicola Antoinette , Maret Corentin , Zhiguo He , Thuret Gilles , Gain Philippe
Published: January 2024

Aims/Purpose: Viability markers are essential for cellular research and tissue transplantation. However, existing options such as Trypan Blue lack specificity, and some clinically used markers are cytotoxic. Therefore, we synthesized the compound F4267, a non‐fluorescent marker that releases fluorescein upon hydrolysis. The aim of this study was to evaluate the quality of F4267 labelling of endothelial cells and its cytotoxicity in immortalized cells and organ‐cultured endothelium.

Methods: We compared the marking capability of F4267 and Calcein‐AM using immortalized cells and endothelium from corneal pairs. The quality of fluorescent labelling was assessed using F4267 at 4 μM and Calcein‐AM at 4 μM. Cytotoxicity of F4267 was evaluated at varying concentrations of 40 and 1000 μM on cells, and at 40 μM on corneal endothelium, with single, repeated, or prolonged exposures. The final density and viability of corneal endothelium were measured using HEC1 staining.

Results: F4267 (40 μM) exhibited fluorescent labelling quality equivalent to Calcein‐AM (4 μM), allowing clear differentiation between living, dying, and acellular areas. In HCE‐2 cells, cytotoxicity was reduced by 19% with F4267 (40 μM) compared to Calcein‐AM (4 μM). Prolonged exposure (24 h) to HCEC‐B4G12 cells showed no cytotoxicity with F4267 (40 and 100 μM), but resulted in destruction of the cell layer with Calcein‐AM (4 μM). F4267 (40 μM) also demonstrated significantly lower cytotoxicity, reducing mortality by 10% (single exposure) and 17% (repeated exposure) in organ‐cultured corneas.

Conclusions: F4267 shows promise as a marker for assessing viable endothelial cells in organ culture, providing a safe alternative to existing markers. Its release of fluorescein with excellent cell tolerance supports its clinical potential. The integration of viable endothelial cell density assessment would enhance the value of corneal banks. Further validation is required, as well as exploration of broader applications.

Reference

1. Pipparelli et al., IOVS 2011.
Advancing in vivo modelling and delivery systems for triplet repeat expansion‐mediated corneal endothelial dystrophy: Implications in Anti‐miR therapy
Authors: Piqueras‐Losilla Diego , Campillo Isabel , Perea‐Galera Laura , López‐Domènech Sandra , Rocha‐Barajas Milagros , Roig‐Revert Maria Jose , Peris‐Martinez Cristina , Barbera‐Fuset Clara , Huguet Aline , Gourdon Genevieve , Llamusí Beatriz , Cerro‐Herros Estefanía
Published: January 2024

Aims/Purpose: Triplet repeat expansion‐mediated endothelial corneal dystrophy, including Fuchs endothelial corneal dystrophy (FECD), is characterized by abnormal expansions of trinucleotide repeats, resulting in corneal endothelium dysfunction [1,2]. This study aims to characterize a reliable in vivo model, that it lacks, and explore the therapeutic potential of anti‐miRs, which have shown efficacy in other disorders involving triplet repeat expansions [3,4,5]. Current invasive delivery methods for eye‐based treatments present challenges, so our focus is on optimizing non‐invasive delivery methods for anti‐miR‐based therapy.

Methods: A transgenic mouse model with a significant CTG repeat expansion (>1000), established in DM1, was investigated as an in vivo model for corneal endothelial dystrophy. The Fuchs‐like phenotype of the disease was characterized using immunohistochemistry and FISH techniques. Delivery methods were explored to enhance the targeting of corneal endothelial cells (CEC). Delivery efficacy and marker expression were assessed using fluorescence, RT‐qPCR, PCR, western blotting, and immunocytochemistry techniques. FECD cell cultures were established to evaluate the challenging FECD‐specific delivery systems.

Results: A novel in vivo model has been characterized for studying corneal endothelial dystrophy caused by triplet repeat expansion, exhibiting similarities to the Fuchs‐like phenotype. Enhanced delivery methods have been identified to improve transfection efficiency in endothelial (HUVEC) and CEC. Successful establishment of FECD cell cultures has allowed the evaluation of these enhanced delivery systems.

Conclusions: The first successful characterization of an in vivo model for triplet repeat expansion‐mediated corneal endothelial dystrophy has been achieved. This model shows potential for assessing the reversal of these phenotypes in the ocular region. Moreover, the successful delivery of new systems across CEC suggests the possibility of non‐invasive administration of anti‐miR directly into the eye. This breakthrough opens the door for future research on anti‐miRs in other diseases caused by triplet repeat expansion, such as FECD.

Reference

In PMID: [1] 28886202, [2] 34130750, [3] 29946070, [4] 32805487, [5] 22764244.
Vitamin D supplementation reduces systemic modulation of oxidative stress and collagen degradation in keratoconus patients
Authors: Suanno Giuseppe , Vitar Romina Mayra Lasagni , Fonteyne Philippe , Knutsson Karl Anders , Bertuzzi Federico , Galli Laura , Rama Paolo , Ferrari Giulio
Published: January 2024

Aims/Purpose: To assess whether vitamin D (Vit D) supplementation modulates systemic biomarkers involved in collagen degradation and oxidative stress in adolescent patients affected with keratoconus (KC).

Methods: This study included forty adolescent patients (age range: 16–19 years) with KC and Vit D insufficiency (<30 ng/mL). The patients were supplemented with vitamin D for 6 months and followed up for additional 6 months (total study duration: 12 months). Blood samples were collected at 1, 6, and 12 months. The levels of Vit D or its receptor (VDR), collagen catabolism (type I collagen degradation product; ICTP), and oxidative stress (Peroxisome proliferator‐activated receptor gamma; PPAR‐γ) were quantified by ELISA or RT‐PCR.

Results: We found that Vit D levels significantly increased at 6 months after supplementation. Moreover, at month 6 the expression of VDR was upregulated (p < 0.01), while collagen degradation (ICTP; p < 0.01) and oxidative stress (PPAR‐γ; p < 0.05) were significantly reduced.

Conclusions: Our findings show that Vit D supplementation reduces oxidative stress and collagen catabolism, which have a key role in KC pathophysiology. These findings provide a potential mechanism by which Vit D could impact KC progression and provide preliminary evidence that KC may be a systemic disease.
Investigation of genes and miRNAs associated with scarless healing in orbital adipose‐derived and limbal‐derived mesenchymal stem cells treated with vitamin C
Authors: Atalay Eray , Eyubova Sevinj , Soykan Merve Nur , Tasa Burcugül Altuğ , Ozalp Onur , Sarıboyacı Ayla Eker
Published: January 2024

Aims/Purpose: In this study we aimed to investigate miRNAs associated with scarless wound healing in limbal‐derived stomal‐mesenchymal stem cells (hLMSC) and orbital adipose tissue‐derived stem cells (hOA‐MSC) treated individually with vitamin C and exosomes obtained after vitamin C treatment.

Methods: Isolation and characterization of hLMSCs and hOA‐MSCs were performed. MTT assay was employed to determine the ideal non‐cytotoxic and proliferative concentration of vitamin C (vit C). The selected concentration was applied to the cell culture medium of hLMSCs and hOA‐MSCs (vit C‐treated) followed by procurement of secreted exosomes (vit C‐exo) and their characterization. These exosomes were then used to enrich cell culture media of naïve hLMSCs and hOA‐MSCs. miR29, miR107, miR155, and miR543 miRNAs and Transforming Growth Factor Beta 1 (TGFβ1), TGFβ3 were analysed by Real‐Time PCR in both vit C treated and vit C‐exo‐treated cells.

Results: Vit C‐exo and vit C‐treated hLMSCs demonstrated slight reductions in TGFβ1 and TGFβ3 expressions compared to controls. In contrast, a modest increase in TGFβ1 and TGFβ3 levels was noted in hOA‐MSCs after vit‐C and vit C‐exo treatment. After vit C‐exo application, expression of miR155 and miR107 increased in hLMSCs and decreased in hOA‐MSCs. An opposite trend was observed with miR543 expression with an increase in hOA‐MSCs and a decrease in hLMSCs. miR29 associated with fibrosis was dramatically increased in hOA‐MSCs, but not in hLMSCs.

Conclusions: In conclusion, we show that miRNA and RNA contents of treated mesenchymal stem cells may vary depending on the origin of tissue. These results suggest that vitamin C could promote a relatively more pronounced anti‐fibrotic character in hOA‐MSCs.

The authors acknowledge the support from Eskisehir Osmangazi University, Scientific Research Projects (ESOGU‐BAP Grant ID: TOA‐2022‐2458).
A higher abundance of butyrate‐producing taxa in the gut is associated with lower glaucoma prevalence
Authors: Vergroesen Joëlle , Jarrar Zakariya , Weiss Stefan , Frost Fabian , Kraaij Robert , Medina‐Gomez Carolina , Amin Najaf , van Duijn Cornelia , Klaver Caroline , Jürgens Clemens , Hammond Chris , Ramdas Wishal
Published: January 2024

Aims/Purpose: Glaucoma is an eye disease that is the commonest cause of irreversible blindness worldwide. It has been suggested that gut microbiota can produce reactive oxygen species and pro‐inflammatory cytokines that may travel from the gastric mucosa to distal sites, such as the optic nerve head or trabecular meshwork. There is evidence for a gut‐eye axis, as microbial dysbiosis has been associated with retinal diseases. Here, we investigated the association between glaucoma prevalence and the gut microbiome. Moreover, we analysed the association of the gut microbiome with intraocular pressure (IOP; risk factor of glaucoma) and vertical cup‐to‐disc ratio (VCDR; quantifying glaucoma severity).

Methods: The discovery analyses included participants of the Rotterdam Study and the Erasmus Glaucoma Cohort. A total of 225 glaucoma patients were matched on age and sex with 1247 participants without glaucoma. Stool samples were collected and used to generate 16S rRNA gene profiles. We assessed associations with 233 taxa. We used data from the TwinsUK and the Study of Health in Pomerania (SHIP) to replicate our findings. The TwinsUK dataset consisted of 32 participants with glaucoma and 1542 unrelated, unmatched participants without glaucoma. The SHIP dataset consisted of a total of 2546 participants.

Results: Several butyrate‐producing taxa (e.g., Butyrivibrio, Caproiciproducens, Clostridium sensu stricto 1, Coprococcus 1, Ruminococcaceae UCG 007, Shuttleworthia) were associated with lower glaucoma prevalence, lower IOP, and smaller VCDR. The replication analyses confirmed the findings from the discovery analyses.

Conclusions: Large human studies exploring the link between the gut microbiome and glaucoma are lacking. Our results support the hypothesis that microbial dysbiosis plays a role in the pathophysiology of glaucoma. This research may support future research into the mediating role of butyrate‐producing taxa in the relation between dietary intake and glaucoma.
Neurodegeneration in diabetic retinopathy: An insight on its main signalling pathways
Authors: Gallego‐Martínez Alex , Andrés‐Blasco Irene , Casaroli Ricardo , Di Lauro Salvatore , Pinazo‐Duran Maria Dolores
Published: January 2024

Aims/Purpose: In the latest years neurodegeneration has been considered as one of the main pathological processes involved in proliferative diabetic retinopathy's (PDR) onset and progression. We aimed to increase the understanding on the role of the main signalling molecules that participate in this phenomenon, including apoptotic, excitotoxic and neurotrophic factor pathways.

Methods: Participants of both sexes were selected and programmed for vitrectomy by its diabetes mellitus 2 (DM2)‐derived vitreoretinal complications (PDR group, PDRG; n = 20), or by suffering macular hole, epiretinal membrane or rhegmatogenous retinal detachment (as the surrogate control group, SCG; n = 26). Vitreous body (VIT) and plasma (PLS) samples were collected and processed to determine the glutamate, caspase‐3 (CAS‐3) and brain‐derived neurotrophic factor (BDNF) levels. Next‐Generation Sequencing (NGS) techniques were applied to characterize the miRNA expression pattern in both groups.

Results: Significantly higher VIT glutamate (p < 0.05) and CAS‐3 (p < 0.05), and significantly lower BDNF (p < 0.05) levels were detected in the PDRG. Significantly higher PLS glutamate (p < 0.05) and CAS‐3 (p < 0.05) levels were found in diabetics. However, PLS levels of BDNF showed no differences between groups (p = 0.80). NGS analysis showed a different miRNA expression pattern between both groups.

Conclusions: Diabetes‐induced changes in retinal neurons/glia may be the key to discover preclinical biomarkers for better managing diabetic eyes. Glutamate, caspase‐3 and BDNF, playing important roles in the neurodegenerative processes occurring in PDR, are pivotal candidates to identify diabetics at high risk of sight‐threatening complications. Additionally, certain miRNAs could be playing an important role in these signalling pathways, being involved in PDR's neurodegenerative phenomenon.
Effect of obesity, dietary habits and physical exercise on visual acuity in healthy young subjects
Authors: Moreira‐Estebaranz Carolina , Remis‐Gonzalez Melisa , Gavilán Beatriz Sánchez , Hidalgo‐Saiz Beatriz , Giudice Luana , Cedrun‐Sanchez Juan , Puell María
Published: January 2024

Aims/Purpose: To explore the effect of obesity, dietary habits, and physical exercise on high‐contrast visual acuity (HC‐VA) and low‐contrast visual acuity (LC‐VA) in healthy young subjects.

Methods: A cross‐sectional pilot study was performed in 64 apparently healthy subjects (mean 21.6 ± 2.2 years of age; 24 men and 40 women). Best‐corrected distance HC‐VA and LC‐VA were measured using logMAR letter charts. Weight, height, and waist circumference (WC) were measured, and body mass index (BMI) and waist‐to‐height ratio (WHtR) calculated. A lifestyle questionnaire was used to investigate weekly physical activity (sedentary, active, and very active), the intake of fruits and vegetables per day (0–1 serving, 2–4 servings and 5 or more servings) and the consumption of saturated fat per day (0–1 serving and 2–4 servings). In addition, systolic (SBP) and diastolic blood pressure (DBP) were measured, and cardiovascular risk (CVR) was calculated using the Framingham calculator.

Results: Mean CVR was normal (3.07 ± 2.2%) and spherical equivalent was −0.55 ± 0.88 dioptres. 7.8% of the subjects was underweight, 57.8% had normal weight (18.5 ≤ BMI < 25), 23.4% overweight (25 ≤ BMI < 30), and 10.9% obesity. Abdominal obesity was normal (WHtR < 0.5) in 76.5% and 23.4% had abdominal obesity (WHtR ≥ 0.5). WHtR and BMI were not significantly correlated with HC‐VA and LC‐VA. No significant differences were found in the means of HC‐AV and LC‐AV between the physical exercise groups and according to the daily intake of fruits and vegetables. In the group consuming higher servings of saturated fat, mean HC‐VA was 0.03 logMAR worse (p = 0.0474) and mean LC‐VA was 0.05 logMAR worse (p = 0.0068) than in the group that reported consuming lower servings of saturated fat.

Conclusions: Obesity, physical exercise and fruit and vegetable consumption were not associated with HC‐VA and LC‐VA. Conversely, higher saturated fat intake was associated with worse HC‐VA and LC‐VA in young adults.
Retina hypoperfusion in multiple sclerosis: Is it only a consequence of atrophy?
Authors: Cerdà‐Ibáñez Marta , Manfreda‐Domínguez Laura , Duch‐Samper Antonio
Published: January 2024

Aims/Purpose: To study if there are vascular changes in patients with multiple sclerosis (MS) when compared healthy controls, analysing oct and OCT‐angiography findings (choroidal thickness and retinal vascular density) at the macular level.

Methods: The study compared two groups (controls and patients) and it analysed whether there were statistically significant differences in the different parameters studied using OCT: choroidal thickness and in the vascular macular plexuses, using OCT‐angiography. Any patient has an optic neuritis history. It was also studied whether there was a statistically significant correlation between anatomical parameters (radial nerve fibre layer, RNFL and ganglion cell layer, GCL) and vascular parameters matching cases and controls by age and sex.

Results: We found a statistically significant reduction in macular choroidal thickness in patients when compared to controls. The study of retinal vascular plexuses showed that the superficial and deep retinal vascular plexuses and the choriocapillaris plexus showed significantly lower vascular density in the patients group. Variations in anatomical parameters between anatomical parameters and in vascular parameters between vascular parameters pairing cases and controls show direct correlations. Regarding the correlation between the differences in anatomical versus vascular parameters, we only observed a low direct correlation between the difference in the papillary RFNL and that of the superficial macular vascular plexus between case and control group.

Conclusions: The density of macular vascular plexus and choroidal thickness proved to be significantly lower in MS patients than in healthy subjects. To date, it is not known to what extent hypoperfusion in MS is a cause or consequence of the brain disease or whether it is a simply association. Vascular parameters could be used as useful markers in the diagnosis and follow‐up of MS.
Anterior optic neuritis associated with clamydia trachomatis prostatitis
Authors: Nicolas Javier Garulo , Domínguez Laura Manfreda , Tepper Sergio Alfredo Maugard , Prades Gemma Ortega , Martínez Julia Pérez , Samper Antonio Duch
Published: January 2024

Aims/Purpose: Parainfectious optic neuritis appears between one and 3 weeks after the onset of an infectious episode of viral or more rarely, bacterial aetiology. Hereby we present a case of bilateral optic disc edema presented during the course of a chlamydia trachomatis prostatitis, which spontaneously resolved after treatment.

Methods: A 32‐year‐old patient who, in a context of a 10 days evolution prostatitis, suffers from a loss on the lower visual field in the right eye (OD) associated with cervical pain, fever and malaise. Ophthalmologic examination reveals bilateral optic disc oedema, and complementary tests show an elevation of C‐reactive protein up to 104 mg/L, visual evoked potentials with increased latency (more in OD) and the incidental finding of bilateral papillary drusen evidenced on computerized axial tomography.

Results: The detection of chlamydia trachomatis DNA in a semen sample leads to an adjustment of antibiotic treatment. A month later, after fully healing of the prostatitis, the resolution of the papillary oedema in both eyes was observed with persistence of a pseudoedema typical of papillary drusen, as well as an improvement of the visual field whose residual affectation is reduced to arciform defects consistent too with the described drusen.

Conclusions: This case has the peculiarity of presenting an optic disc oedema superimposed on a pseudoedema by papillary drusen. Although choroiditis has been described as a rare ophthalmic manifestation of systemic chlamydia trachomatis infection, there is no previous literature describing optic neuritis. In our patient, the proposed pathogenic mechanism is a parainfectious autoimmune reaction whose prognosis is excellent.

References

1. Chronic Ocular Chlamydia Trachomatis Infection in Rabbits. Boiko et al, 2014.

2. Inflammatory Optic Neuritis. Ayuso et al, 2009.

3. Optic Disc Drusen: a Systematic Review. Allegrini et al, 2020.
Papillophlebitis: A case series of a controversial diagnosis
Authors: Shamsher Ehtesham , Kawasaki Aki
Published: January 2024

Aims/Purpose: Papillophlebitis refers to an isolated optic disc oedema with venous engorgement in asymptomatic patients as defined by Walsh and Hoyt in 1969. We report a case series of 3 patients who developed papillophlebitis related to SARS‐CoV‐2 vaccination, type 2 diabetes or idiopathic. A literature review was also performed.

Methods: Observational case report of 3 patients and a review of the literature covering papillophlebitis cases was performed using Pubmed, Embase and Web of Science. Cases presenting with visual loss, RAPD, visual field defect or retinal vascular occlusion were excluded.

Results: We report the case of 3 patients who did not have any visual complain and presented a unilateral optic disc oedema found by chance. The 1st patient was 33 year‐old and her past medical history was significant for SARS‐Cov‐2 vaccination. The 2nd patient was 6 year‐old and in general good health. The 3rd patient was known for a type 2 diabetes with no complications. For all patients, the visual acuity was 1.0, the intraocular pressure was normal, the anterior segment was quiet and the fundus showed a unilateral optic disc oedema without any haemorrhage. The RNFL OCT confirmed the presence of an optic disc oedema. The visual field was normal. An extensive blood test was negative for auto‐immune, inflammatory and vascular disease. In our patients, the optic disc oedema decreased spontaneously after a couple of months without any treatment and they retain 1.0 vision. A diagnosis of papillophlebitis was made. In the literature, the term papillophlebitis is not well‐defined and controversial. No treatment is required, and the condition resolved spontaneously over time. The visual prognosis is excellent as patients keep a 1.0 vision with a normal visual function. No recurrence has been reported.

Conclusions: Papillophlebitis is diagnosed after ruling out any inflammatory, infectious or auto‐immune disease in asymptomatic patients who present a spontaneous recovery without any treatment as reported in our cases.
Breaking the mould: An essential need in optic neuritis management
Authors: Martí M. Ángeles Ruth Bort , Fustel Paula Boned , García Laura Fernández , Estruch Bonaventurs Casanova
Published: January 2024

Aims/Purpose: To present a clinical case to highlight the importance of ophthalmological examination in the management of optic neuritis.

Methods: Case report.

Results: A 45‐year‐old woman with Sjögren's syndrome and a family history of MS presents to the emergency department. She complains of decreased vision OD for the past 4 days, with exacerbated‐by‐eye‐movements retroocular pain and migraine‐like headache. BCVA is amaurosis OD and 1 OI, with right RAPD and no colour vision impairment in OI. Except for optic disc oedema with splinter haemorrhages in OD the rest of the ophthalmological examination is normal. RNFL‐OCT reveals thickening in the OD (220 μm/110 μm). Brain CT and laboratory tests, including D‐dimers, are normal. A LP is performed to rule out infectious causes is normal. Neurofilament and ESR are also normal. Brain and spinal MRI show no abnormalities. Due to the severity, methylprednisolone therapy is initiated. One week later, her symptoms are stable, except for headache and retroocular pain improvement. Upon reassessment, despite preserved BCVA and Ishihara in OI, an increase in RNFL thickening is noted in OI (120 μm), with partial arcuate defect in visual field. Anti‐MOG, AQP4 and a panel of autoantibodies including anti‐Ro and anti‐La, are still pending. Considering the bilateral involvement, plasma exchange therapy is initiated. 14 days after, BCVA OU has improved to 1, and the visual field and Ishihara test have normalized. RNFL thickening is still observed OU (161/120 μm) and there is persistent optic disc edema OD. Anti‐MOG are positive, AQP4‐Ab are negative, and both negative in CSF.

Conclusions: The coexistence of other autoimmune diseases, can lead to attributing the ON to that disease rather than considering the neuroinflammatory aetiology, leading to delayed diagnosis. The detection of subclinical bilateral involvement was crucial in escalating the therapeutic regimen. Seropositivity is the confirmatory diagnostic marker, but in many centres, it may be difficult to obtain reliable biomarker data.
A review of retinal analysis by OCT in murine models Alzheimer's disease
Authors: Sanchez‐Puebla Lidia , López‐Cuenca Inés , de Hoz Rosa , Ramirez Ana Isabel , Matamoros José A. , Lozano María Pilar Rojas , Salobrar‐Garcia Elena , Fernández‐Albarral José A. , Vázquez Alberto Arias , Salazar Juan Jose , Ramirez Jose Manuel
Published: January 2024

Aims/Purpose: The use of murine models of Alzheimer's disease (AD) in the study of its pathophysiology is essential. In addition to a histological study of the retina, optical coherence tomography (OCT) allows a cost‐effective in vivo analysis of the retina. However, there is no standardization in the use of OCT in murine models of AD, leading to significant variations in study results. A review of the literature on murine models of AD analysed by OCT has been carried out. The characteristics of the animal model, the types of OCT, the retinal sectors analysed, the segmentation layers and the software used for segmentation were examined.

Methods: We performed a literature search up to April 2023 using “MESH” terms in PubMed. The terms used were: “Alzheimer's mouse model”, “Optical Coherence Tomography”, “retinal optical coherence tomography” … as well as their combinations. We filter the articles by author criteria: the terms had to be in the title, in the abstract or in the article and they should be written in English or Spanish. Finally, 76 articles were used to the manuscript.

Results: In comparison to studies using OCT in AD patients, only fourteen studies have utilized this technique to examine the retinas of murine AD models. Six different models, both first and second generation, were analysed, with most featuring presenilin mutations. There is no consensus regarding the measuring instrument, retinal area analysed, segmentation techniques, or software employed for analysis. Although some authors used the same OCT device, variations in other parameters hinder direct result comparison.

Conclusions: It is essential to establish a unified criteria for OCT analysis of the retina in murine models of AD. This would allow the comparison of results and the establishment of measurement protocols. The use of OCT to understand the pathophysiology of AD would facilitate the longitudinal analysis of the disease and the possible identification of biomarkers.
Uncorrected refractive errors in Senegalese school‐aged children
Authors: Galindo‐Romero Caridad , Ordoñez‐Angamarca Luis , Berrio Esther , Villegas Eloy A.
Published: January 2024

Aims/Purpose: To assess the visual health and the prevalence of visual impairment (VI) due to uncorrected refractive errors, the most common cause of VI in developing countries, in Senegalese school‐aged children.

Methods: Through the campaign carried out by the Spanish NGO “Azul en Acción” in Senegal (Africa), a total of 235 children aged 6–14 years from four schools were examined. Ocular abnormalities and uncorrected distance visual acuity (VA) were analysed and VI was defined as presenting visual acuity worse than 0.3 logMAR in any of the eyes (Bourne et al. 2022). In children with VA worse than 0.3 logMAR, refractive error was measuring by retinoscopy and subjective refraction and defined using spherical equivalents (SE).

Results: A total of 235 Senegalese children aged from 6 to 14 years (mean ± SD, 8.7 ± 2.4 years‐old) were examined. Of them, 15.3% of the children (N = 46) were affected of VI, most of them due to uncorrected refractive errors, easily resolved with spectacles (N = 37, 76.9%). The mean value of SE was +0.42 ± 1.18 D, with myopia as the least frequent ametropia (N = 13, 29.7%). Only 9 VI‐children did not improve the VA with optical prescription and were referred to hospital for a whole ocular examination.

Conclusions: The prevalence of VI in Senegalese children is very low, as well as the incidence of infant myopia compared to developed countries (Sankaridurg et al., 2021). However, little was known about visual health in Senegalese children and this results confirm the need for early eye care practitioner interventions in developing countries to prevent and treat VI due to uncorrected refractive errors.

References

1. Bourne RRA, Cicinelli MV, Sedighi T et al. Effective refractive error coverage in adults aged 50 years and older: estimates from population‐based surveys in 61 countries. Lancet Glob Health 2022; 10: e1754‐e1763.

2. Sankaridurg P, Tahhan N, Kandel H et al. IMI Impact of Myopia. Invest Ophthalmol Vis Sci 2021; 62: 2.
Optic neuritis post SARS‐CoV‐2 infection and vaccination; a systematic review exploring the clinical features of optic neuritis after SARS‐CoV‐2 infection and vaccination
Authors: Georganta Iliana , Chasapi Despoina , Smith Charlotte , Kopsidas Konstantinos , Tatham Andrew
Published: January 2024

Aims/Purpose: This study aims to characterize the symptoms and clinical features of Optic Neuritis (ON) following SARS‐CoV‐2 infection and vaccination.

Methods: A literature search was conducted in 4 databases (Pubmed, Medline, Embase, Google Scholar) to identify relevant case reports and case series. The records were screened and articles adhering to the inclusion criteria were critically appraised.

Results: Sixty‐eight studies were found to be eligible for inclusion, including 34 reporting ON following SARS‐CoV‐2 infection and an equal number reporting cases post vaccination. In total 93 patients and 125 eyes were included. The infection cohort included 42 patients and 56 eyes, 48.8% were female and 33.3% experienced bilateral ON. The mean visual acuity was 1.64 LogMAR, while pain was present in 75%. Oligoclonal bands were present in 3 patients, MOG antibodies in 18, and AQP‐4 antibodies in 4. The vaccination cohort included 51 patients and 69 eyes. 60.8% were female and 35.3% had a bilateral ON. The mean visual acuity was 0.93 LogMAR. Oligoclonal bands were present in 46.7%, MOG antibodies in 9 patients and AQP‐4 antibodies in 3.

Conclusions: Patients with ON post SARS‐CoV infection were more likely to experience severe visual impairment than in cases following vaccination. Further research is required to outline the clinical features of ON after COVID‐19 infection and vaccination, and establish causality.