bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of pathogenesis of the pterygium by transcriptomic and proteomic analysis
Authors: Kim Chang Hwan , Ji Yong Woo
Published: January 2024

Aims/Purpose: Extrinsic factors, including ultraviolet rays, are well‐known risk factors in the pathogenesis of pterygia. However, the biomolecular intrinsic factors that could serve as therapeutic targets have not been fully elucidated. Therefore, this study aimed to investigate comprehensive changes in the proteome and transcriptome of conjunctival pterygium tissues from human patients using multi‐omics analysis.

Methods: A prospective cross‐sectional study enrolled 30 patients diagnosed with pterygium who underwent surgery from May 2020 to December 2020. During surgery, normal conjunctiva and conjunctival tissues with pterygium were collected. Nano liquid chromatography with tandem mass labelling spectrometry and next‐generation sequencing were performed on the obtained specimens. Proteins with significantly expressed mRNAs between pterygium and control were identified, and their biological processes were analysed using bioinformatic tools.

Results: Through the integration of transcriptomic and proteomic analyses, a total of 1288 proteins were identified, which were also confirmed by mRNA expression. Hierarchical clustering heatmap analysis revealed distinct clusters corresponding to each group, and principle component analysis demonstrated a prominent separation between groups. Among the identified proteins, 185 were determined as differentially expressed proteins (DEPs), with 154 upregulated and 31 downregulated in pterygium compared to the control group. Protein–protein interaction network analysis revealed six distinct interconnected networks of DEPs, and gene ontology enrichment analysis highlighted biological processes associated with extracellular matrix organization, insulin‐like growth factor‐related pathways, and the immune system.

Conclusions: This study demonstrates proteomic alterations in conjunctival tissues of patients with pterygium, which are corroborated by RNA expression analysis. The identified significant proteins in pterygium are associated with specific biological pathways and could be potential therapeutic targets. The integrated proteo‐transcriptomic analysis provides essential insights into the pathogenesis of pterygium, contributing to the identification of novel treatment strategies.
Decellularized human corneal lenticule as a delivery system of recombinant human nerve growth factor and human amniotic fluid stem cells factors for posterior ocular disease treatment
Authors: Mandatori Domitilla , Pelusi Letizia , Ghelardoni Maddalena , Agnifili Luca , Di Pietrantonio Nadia , Hurst Jose , Allegretti Marcello , Schnichels Sven , Mastropasqua Leonardo , Bollini Sveva , Nubile Mario , Pandolfi Assunta
Published: January 2024

Aims/Purpose: Posterior ocular diseases, such as glaucoma and diabetic retinopathy (DR), are the main causes of blindness worldwide. Among the possible therapeutic approaches particular interest was turned to neurotrophic factors, such as Nerve Growth Factor (NGF), and to mesenchymal stem cells (MSCs)‐derived factors. Nevertheless, the local drugs and factors delivery in the eye remains a challenge. Therefore, using an in vitro model of glaucoma and an ex vivo model of DR, this study aimed to test the feasibility to use decellularized human corneal lenticule (hCL) as natural delivery system able to vehicle neurotrophic and MSCs‐regenerative factors.

Methods: hCLs (thickness 100–120 μm) collected from donors undergoing refractive surgery, were decellularized (0.1% SDS) and engineered with MSCs from human amniotic fluid (hAFSCs) and/or with microparticles containing rhNGF (rhNGF‐MPs). Human Trabecular Meshwork cells (HTMCs), damaged with Transforming Growth Factor‐β2 (TGF‐β2; 5 ng/mL for 4 days), were employed to mimic glaucoma condition in vitro. DR disease was reproduced using an ex vivo model of porcine retinal explants exposed to high glucose (HG; 25 mM for 4 days).

Results: Results deriving from glaucoma model showed that the deposition of extracellular matrix and the specific protein expression of COL4a1, COL1a1 and ACTA1 were reduced following the HTMCs incubation with hCL engineered with hAFSCs or rhNGF‐MPs. Likewise, in the DR model, the HG‐increased Tumour Necrosis Factor α (TNF‐α) and Nuclear factor erythroid 2–Related Factor 2 (NRF2) levels were reduced following the incubation with hCL engineered with hAFSCs and rhNGF‐MPs. Of note, as demonstrated by the increase of structural (TUBB3 and Rho) and apoptotic (BAX/Bcl2 and p21) markers, a neuroprotective effect of engineered‐hCLs was observed in the DR model.

Conclusions: Overall, our results demonstrated that this innovative bio‐engineered scaffold may represent a potential therapeutic approach for posterior ocular diseases treatment.
Comparison of waveform‐derived ORA parameters in clinical keratoconus, subclinical keratoconus and healthy subjects
Authors: Atay Kubra , Özalp Onur , Atalay Eray
Published: January 2024

Aims/Purpose: The aim of this study was to comparison of waveform‐derived Ocular Response Analyser (ORA) parameters in clinical keratoconus (KC), subclinical keratoconus (SKC) and healthy subjects.

Methods: This retrospective comparative case series study included 24 eyes with SKC, 24 eyes with KC and 48 eyes of age‐ and sex‐matched healthy subjects. Keratoconus diagnosis was based on clinical examinations, and Scheimpflug corneal tomography. SKC was defined as the presence of the following: (1) normal biomicroscopic findings and topography; (2) anterior (≤7 μm) and posterior (≤16 μm) elevation difference map marked green or yellow; (3) mean keratometry <47D; (4) BAD‐D value <3 SD and (5) keratoconus in the fellow eye. Thirty‐seven parameters derived from the waveform signal obtained with ORA were analysed. The Kruskal‐Wallis H test with Bonferroni correction was used for comparisons. p < 0.05 was considered statistically significant.

Results: While the rate of females in all groups was 33.3%, the mean age was 25.6 ± 0.9, 25.8 ± 1.3 and 25.7 ± 0.8 years in KC, SKC and healthy subjects, respectively. Statistically significant differences between KC and healthy eyes were found in p1area (p = 0.005), p2area (p < 0.001), w1 (p = 0.001), w2 (p = 0.002), path1 (p = 0.032), path2 (p < 0.001), aplhf (p = 0.018), p1area1 (p = 0.021), p2area1 (p < 0.001), w11 (p = 0.028), w21 (p = 0.001), and path21 (p < 0.001). While there were significant differences in w2 (p = 0.016), w21 (p = 0.042), and path21 (p = 0.033) parameters between SKC and healthy eyes, no significant difference was found between SKC and KC eyes.

Conclusions: Approximately one‐third of the waveform‐derived ORA parameters can be used to differentiate between KC and healthy subjects. Parameters derived from the second applanation signal of ORA were superior in distinguishing SKC from healthy subjects.
Diagnostic errors and delay of keratitis fugax hereditaria
Authors: Immonen Annamari , Kawan Sabita , Backlund Michael , Saaren‐Seppälä Heikki , Kivelä Tero , Turunen Joni
Published: January 2024

Aims/Purpose: To chart misdiagnoses associated with keratitis fugax hereditaria (KFH), an autosomal dominant periodic corneal autoinflammatory disease, and the frequency of misdiagnosed KFH in patients diagnosed with unspecified anterior uveitis, herpes keratitis, or unspecified keratitis.

Methods: Charts of patients with genetically confirmed KFH (n = 94) were reviewed. Two Finnish biobanks provided 2037 DNA samples meeting the inclusion criterion of a diagnosis KFH can be misdiagnosed with and the exclusion criterion of having a common underlying cause of anterior uveitis, such as rheumatoid arthritis. The NLRP3 c.61G>C variant was detected using restriction fragment length polymorphism analysis, and Sanger sequencing for confirmation. Age, sex, ocular and other diagnoses, and laboratory results were collected from patients carrying the variant.

Results: The time between first symptoms and the diagnosis of KFH ranged from 0 to 62 years (median, 21; interquartile range [IQR], 8–45). Analysis of patient charts revealed that the most common misdiagnoses were acute anterior uveitis (51% of all misdiagnoses/26% of all patients), conjunctivitis (26%/13%), or recurrent erosion (21%/11%). A mild anterior chamber inflammation was observed in 30% of patients, 0.5+ or 1+ by Standardization of Uveitis Nomenclature (SUN) criteria. Of the biobank samples, 12/2037 (0.59%; 95% confidence interval [CI] 0.56%–0.61%) carried the c.61G>C variant: 11 diagnosed with anterior uveitis, and one with unspecified keratitis. Three had previously been diagnosed with KFH. The age range of the 12 variant carriers varied from 38 to 79 (median, 63; IQR, 48–76) with nine females and three males.

Conclusions: KFH is most frequently misdiagnosed as anterior uveitis. In Finland, it might be beneficial to add testing for the NLRP3 c.61G>C variant in existing laboratory test packages for anterior uveitis.
Mechanotransduction and corneal endothelium homeostasis: Application in tissue engineering
Authors: Hussain Noor Ahmed , Figueiredo Francisco , Connon Che
Published: January 2024

Aim: Globally, there is a significant shortage of corneas available in the eye banks. This high demand has triggered a new platform for addressing the issue by using biomaterials. Mechanical cues play a key role in regulating fundamental cellular functions, as demonstrated by numerous studies conducted on many types of cells. This project's goal is to engineer an effective Descemet's membrane (DM) by changing the stiffness of compressed collagen scaffolds so that it maximizes the functional properties of Descemet's membrane to fully support endothelial cells.

Methods: This study entails creation of collagen substrates of varying stiffness which enabled to scrutinize the effect of different biomechanical signals on human corneal endothelial cells (HCECs) behaviour. Thereafter, the viability, function, and responses of HCECs were compared to determine the best scaffold to support corneal endothelial cells. Collagen scaffolds were characterized: light transmittance, scaffold stiffness values, and surface topography by Atomic Force Microscope. Studying HCECs' responses and behaviour on scaffolds of different stiffness has been done by assessing the cell viability and immunofluorescence labelling for Yes‐associated protein (YAP), ZO‐1, and Na/K ATPase.

Results: The study found higher growth rate of stiff scaffolds and a confluent monolayer of HCECs in comparison to soft scaffolds. This was accompanied by an increase in nuclear YAP. Typical functional markers were expressed by HCECs on a stiff collagen scaffold compared to a softer scaffold. Collagen scaffolds with a different stiffness do affect nuclear YAP, therefore demonstrating mechanosensitivity of corneal endothelial cells.

Conclusion: In conclusion, these results convey that tissue engineering of the human corneal endothelium can determine the scaffold which mimics the best DM biomechanical properties. Hence, very soon scaffold improvements is viable if the role of mechanotransduction is explained for endothelial cell homeostasis.
Peripheral sterile corneal infiltrate after cross linking in keratoconus: A case report
Authors: Ayad Rima , Ghizlane Daghouj , Chahir Roukaya , Ajdour Lamiaa
Published: January 2024

Aims/Purpose: The aim of our work is to describe the clinical aspect of sterile corneal infiltrates after cross linking and to evaluate the risk factors involved in their occurrence.

Methods: We report the case of a young girl, followed for bilateral keratoconus having made a cross linking which was complicated by sterile catarrhal infiltrates.

Results: This is a 15 years old girl, followed for allergic conjunctivitis with notion of self‐medication. The ophthalmological examination on admission found a visual acuity with correction counting fingers at 1 metre in oculus uterque (OU), some conjunctival papillae, minimal blepharitis, clear cornea, cortico‐nuclear cataract ocular tone was 10 mmHg in OU, normal fundus in OU. A corneal topography was performed showing signs of bilateral keratoconus classified as stage III according to the Krumeich classification. An emergency cross linking was indicated in OU starting with the OL, the patient was put on a topical antibiotic treatment, artificial tears with a daily control. At 4 days post‐op, the cornea had completely re‐epithelialized with the presence of a slight central haze and the appearance of 2 inferior stromal opacities of 1 mm/1 mm associated with a crescent infiltrate and 2 similar superior stromal opacities taking the fluorescent in front of the free edge. A corneal swab was taken for bacteriological, mycological and parasitological study and came back negative. The patient was initially put on ceftazidime and vancomycin based eye drops with a blepharitis treatment based on azyter collyrium lavage and artificial tear. The examination 48 h later showed persistence of stromal opacities without taking fluo. A local corticosteroid therapy was started with strict monitoring. The evolution was marked by an almost total regression of the stromal opacities and a disappearance of the central haze. The diagnosis of sterile infiltrate was made in view of the marked clinical improvement under local corticosteroid therapy and the absence of germs in the corneal sample.

Conclusions: Evaluation of risk factors showed that epithelial injury may be the common pathway in pathogenesis, as no sterile infiltrate in Epi‐on CXL occurred, and postoperative NSAIDs use increased the risk of developing sterile infiltrates approximately fourfold.
Herpetic keratouveitis: A three year follow‐up case
Authors: Arun Kirupakaran , Georgoudis Panagiotis
Published: January 2024

Aims/Purpose: Herpetic keratouveitis1 is a common presentation to Eye Casualty but due to the broad spectrum of manifestations that it can present with, it is an easy diagnosis to miss. The aim of this report is to create awareness among ophthalmologists of how this disease can present, appropriate clues to the diagnosis as well as how it should be managed.

Methods: A 76 year old male presented to the eye emergency department with a 1 week history of significant visual deterioration (6/90 pinhole), redness and photophobia in his left eye. He was initially treated 6 weeks prior with a course of tapering steroid drops for presumed acute anterior uveitis which led to an initial improvement in symptoms, followed by a sudden worsening of symptoms. Ocular examination revealed a 9 mm × 8 mm central corneal ulcer with a satellite lesion superonasally, Descemet folds, reduced corneal sensation with mild anterior chamber inflammation and no posterior segment pathology. Corneal scrapes as well as PCR was sent for culture and sensitivity.

Results: PCR revealed a positive result for herpes simplex virus and the patient showed significant improvement with oral acyclovir, topical gancyclovir ointment and topical steroid drops. In the 3 years following the initial presentation, the patient has had 3 further episodes of left herpetic keratouveitis and has now been put on lifelong maintenance dose oral acyclovir and FML drops.

Conclusions: We report this case to highlight the key clinical features compatible with herpetic keratouveitis. This disease can be chronic and should be considered in any patient presenting with chronic anterior uveitis not improving with steroid drops. PCR remains the gold‐standard for diagnosis however this is not always positive and clinical diagnosis remains key.

Reference

1. Cunningham E.T. Diagnosing and treating herpetic anterior uveitis. Ophthalmology 2000; 107(12: 2129–30. doi:10.1016/s0161‐6420(00)00287‐6.
In‐vivo evaluation of corneal collagen fibrils pattern to detect Keratoconus
Authors: Ancona Chiara , Passaro Maria Laura , Airaldi Matteo , Lipari Eugenio , Semeraro Francesco , Kaye Stephen B. , Romano Vito
Published: January 2024

Aims/Purpose: The corneal stroma, is formed by fibrous connective tissue containing collagen fibrils that are super‐organized in lamellae. In keratoconus (KC), intra‐lamellar and inter‐lamellar disrupted organization causes a progressive thinning and corneal ectasia. The LUMAXIS is a new medical device specifically designed to evaluate the effects of the interaction between polarized light and corneal stroma. It identifies the orientation of collagen fibrils in the cornea, highlighting ultrastructural changes of the tissue. The purpose of this study was to employ the LUMAXIS to discriminate changes in the pattern of corneal collagen fibrils to detect keratoconus.

Methods: Patients with KC and controls were included in this prospective study. Corneal tomography (Pentacam) was acquired as well as polarimetric interferometry (LUMAXIS, Phronema S.r.l., Bari, Italy). Custom software was developed to improve the visualization of the representative cross by extracting the histogram equalized luminance to provide a numerical outcome. We then fit a set of ellipses to the image in a semi‐automatic approach, aiming to capture the boundaries of the iris, pupil, each four quadrants of the cross, and eyelids. Combining this information, we are able to obtain a cross parameter. A correlation between cross outcome and Kmax was calculated.

Results: A total of sixty eyes of sixty patients were included: 30 healthy subjects (including 60 eyes, mean age of 38.0 ± 13.2 years) and 30 patients with KC (60 eyes, mean age of 39.2 ± 12.9 years). Maximum keratometry value were 59.4 ± 11.2 D in the KC group and 45.3 ± 0.8 D in the healthy group. The cross parameter was 0.41 ± 0.028 in the KC group and 0.24 ± 0.055 in the healthy group. Using only measures taken from the cross resulting from the Lumaxis scan, we were able to distinguish between KC and healthy eyes.

Conclusions: The interferometric analysis of diffractive and polarizing effects related to the birefringent properties provides new morphological information at corneal fibrils level. A different corneal pattern of corneal collagen fibrils can be recognized in keratoconus patients compared to healthy patients.
Flap amputation for the diagnosis and treatment of acanthamoeba keratitis: A case report
Authors: Usuga Juan Cadavid , Velez Mauricio , Usuga Maria Ortiz , Perdomo Camilo Restrepo , Izquierdo Luis
Published: January 2024

Aims/Purpose: To report a laser assisted in situ keratomileusis (LASIK) flap amputation as both diagnostic and therapeutic tool in a case of Acanthamoeba keratitis, in a scleral contact lens patient.

Methods: Case report and literature review.

Results: Acanthamoeba keratitis is a serious sight‐threatening infection, which imposes a considerable diagnostic and therapeutic challenge to the ophthalmologist. We report a case of a 38 years old male with post‐LASIK ectasia who was using scleral fitted contact lenses; as he developed keratitis, who had unspecific symptoms such as tearing, photophobia, burning sensation, foreign body sensation and decreased vision. His LASIK flap was surgically amputated as both diagnostic and therapeutic procedure. Histopathology analysis revealed abundant acanthamoeba cysts (Figure 1: Intact intrastromal Acanthamoeba cysts (arrow). Right (R): HE x 400 and left (L): Gomori Methenamine‐Silver Stain ×400). After diagnosis, treatment initiated with 0.2% Chlorhexidine, Propamidine Isothionate and systemic Voriconazole, observing resolution of the infiltrate and complete epithelization within 1 week. At 1 month postoperative, the patient developed symptoms secondary to medications without changes in his visual acuity; Fluorometholone drops were added to the anti‐amoebic treatment, which was continued for six more months.

Conclusions: Corneal Flap amputation is a reasonable option as a diagnostic and therapeutic aid in the management of Acanthamoeba keratitis in patients with past history of LASIK.

Figure 1

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Figure 1
Prevalence and associations of keratokonus among children, adults and elderly in the population‐based ural eye studies
Authors: Panda‐Jonas Songhomitra , Mukharram Bikbov , Gyulli M. , Gilmanshin Timur , Jonas Jost , Iakupova Ellina , Fakhretdinova Albina , Tuliakova Azaliia , Iulia A. , Leisan Gilemzyanova , Khakimov Dinar Dinar A. , Miniazeva Liana
Published: January 2024

Aims/Purpose: To estimate prevalence and associations of keratoconus in populations in Russia with an age from childhood to seniority.

Methods: The study population consisted of the cohorts of three population‐based studies performed in urban and rural areas within the same geographical region in Bashkortostan/Russia: The Ural Children Eye Study (UCES; age: 6–18 years; n = 4890), Ural Eye and Medical Study (UEMS; age: 40+ years; n = 5314) and Ural Very Old Study (UVOS; age: 85+ years; n = 651). Based upon Scheimflug imaging, keratoconus was defined by a keratometric reading of ≥48 D in any eye.

Results: The mean maximal and minimal corneal refractive power increased from the UCES (43.58 ± 1.50 dioptres (D) and 42.70 ± 1.42D, respectively) to the UEMS (44.26 ± 1.70 D and 43.61 ± 1.76D, resp.) and to the UVOS (45.1 ± 1.72D and 43.98 ± 1.68D, resp.). Correspondingly, keratoconus prevalence increased from the UCES (42/4890; 0.086%; 95% CI: 0.060, 0.112) to the UEMS (112/5314; 2.11%; 95% CI: 1.72, 2.49) and to the UVOS (42/651; 6.45%; 95% CI: 4.56, 8.34). In the UCES, higher keratoconus prevalence was associated (multivariable analysis) with higher birth order (OR: 2.34; 95% CI: 1.32, 4.15; p = 0.004), lower birthweight (OR: 0.99; 95% CI: 0.99, 0.99; p < 0.001), and shorter axial length (OR: 0.15;9 5% CI: 0.08, 0.30; p < 0.001). In the UEMS, keratoconus prevalence correlated with shorter axial length (OR: 0.15; 95% CI: 0.10, 0.23; p < 0.001), larger corneal volume (OR: 1.17; 95% CI: 1.09, 1.25; p = 0.001), thicker lens (OR: 2.27; 95% CI:1.06, 5.28; p = 0.04), cortical cataract degree (OR: 1.02; 95% CI:1.01, 1.04; p = 0.01), and higher stage of age‐related macular degeneration (OR: 1.65; 95% CI: 1.09, 2.51; p = 0.02). In the UVOS, keratoconus prevalence correlated with lower educational level (OR: 0.84; 95% CI:0.71, 0.99; p = 0 0.04) and lower dynamometric hand grip force (OR: 0.92; 95% CI: 0.88, 0.97; p = 0.003).

Conclusions: In this study on multiethnic groups from Russia, keratokonus prevalence increased from the paediatric group (0.09%) to the adult group (2.11%) and seniority group (6.45%), correlated mostly with biometric ocular parameters, and was in all age groups statistically independent of most systemic parameters.
Conjunctival vessel density as inflammatory ocular surface marker in systemic autoimmune disease
Authors: Aragona Emanuela , Arrigo Alessandro , Perra Cristian , Miserocchi E. , Modorati Giulio , Bandello Francesco
Published: January 2024

Aims/Purpose: Autoimmune diseases are characterized by a pro‐inflammatory environment, with over‐release of chemokines, as IL‐6, IL‐1β and TNFα. These might have a pro‐vasodilation effect at a conjunctival level, with the clinical result of hyperaemia. Hyperaemia is hardly evaluable from a research point of view. The aim of this study is to investigate the use of conjunctival vessel density (CVD) as a marker of vessel dilation and, indirectly, of ocular surface inflammation, in a cohort of patients affected by autoimmune diseases.

Methods: Study design: cross‐sectional, observational. CVD score was obtained analysing vessel‐enhanced images obtained by R‐scan module of Keratograph 5M (OCULUS Optikgeräte GmbH, Wetzlar, Germany). Images were loaded in ImageJ software package and in‐house scripts were used to analyse CVD at baseline and at follow‐up visit. CVD was obtained through the same methodology widely used in retinal research to study macular vessel density. Clinical data were collected and the correlations were reported.

Results: We collected data from a cohort of patients suffering from autoimmune diseases. All the eyes were categorized considering both systemic and topic treatments, co‐existence of more autoimmune disorders, clinical signs and severity of dry eye. CVD values resulted significantly correlated with dry eye severity, in particular the higher was dry eye severity score, the higher was CVD (p < 0.05).

Conclusions: CVD is a new quantitative metric to objectively measure conjunctival hyperaemia; this diagnostic methodology resulted highly feasible to be performed in clinical practice, without inducing patients' distress, and resulted a parameter highly correlated with the pro‐inflammatory status of the patients.

Reference

1.Singh RB, Liu L, Anchouche S, Yung A, Mittal SK, Blanco T et al. Ocular redness ‐ I: Aetiology, pathogenesis, and assessment of conjunctival hyperemia. Ocul Surf 2021.

2. Wu S, Hong J, Tian L, Cui X, Sun X, Xu J. Assessment of Bulbar Redness with a Newly Developed Keratograph. Optom Vis Sci 2015.

3. Arrigo A, Aragona E, Saladino A, Amato A, Bandello F, Battaglia Parodi M. The impact of different thresholds on optical coherence tomography angiography images binarization and quantitative metrics. Sci Rep 2021.
Our experience in managing patients with dry eye syndrome
Authors: Boieva Yuliia , Bezditko Pavel , Ivzhenko Liudmyla , Shelenkova Anastasiia
Published: January 2024

Aims: To confirm the effectiveness of a comprehensive approach to the treatment of patients(PT) with moderate and moderate severity of dry eye syndrome (DES).

Methods: 53 PT (106 eyes) with 2 and 3 stages of DES aged from 25 to 52 years were included in the examination. The control group (I gr) included 19 PT, in the studied group (II gr)–29 PT. In addition to the standard ophthalmological examination, the PT underwent a Schirmer's test (SCH), Symptomatic Break –Up Time (SBUT), compression test to assess the secretory capacity (Korb, 2005) of the meibomian glands(MG) (using a glass rod) and Ocular Surface Disease Index Questionnaire (OSDI). The TFOS DEWS II report was used to classify the stage of DES. The inclusion criteria: PT with the SCH‐values ≥3 mm, without systemic diseases, the degree of violation of the excretory ability of the MG corresponded to stages 1 and 2. PT of the II gr were offered complex treatment:1‐instillation of drops with hyaluronic acid 5 times a day; 2‐in 2–3 min use of drops with the LIPITECH system; 3– a carbomer‐gel once at night;4‐systematic massages of the eyelids a course of 5–10 sessions over 1.5 months. PT of the I gr continued to use artificial tears min 3 times a day. Control was at 2, 4 and 6 weeks.

Results: Positive dynamics are noted in the II gr for all 4 control indicators. The average indicative of SCH increased by 54.7% (7.5 ± 0.04 mm), SBUT improved by 35.6% (3.6 ± 0.01 s), the duration (time from the beginning) of meibum evacuation decreased by 37.7% (2.3 ± 0.08 s); the OSDI decreased by 54.8% (38.0 ± 0.1) (p < 0.05). The I gr: SCH increased by 20.8% (1.5 ± 0.01 mm), SBUT improved by 12.6% (0.9 ± 0.09 s), the duration of meibum evacuation decreased by 5.7% (0.4 ± 0.04 s); the OSDI‐36.2% (24.9 ± 0.7) (p < 0.05).

Conclusions: With a comprehensive approach to the problem and the patient's understanding of the need to comply with all recommendations, it is possible to achieve a prolonged positive result of treatment, and to preserve this effect in the future.
Regenerative medicine in pterygium surgery
Authors: Palarie Natalia , Natalia Palii
Published: January 2024

Aims/Purpose: Pterygium is a frequently occurring eye condition that arises due to excessive cellular growth, resulting in the development of abnormal fibrovascular growth of the conjunctiva. Despite the improvement of surgical techniques, preventing postoperative recurrence continues to be a significant challenge. At present, pterygium excision using conjunctival autograft is the preferred surgical method, however there is no universally accepted technique to completely eliminate the risk of pterygium recurrence. Plasma rich in growth factors (PRGF) is an autologous blood product rich in proteins and growth factors which can be rapidly obtained from patient blood. Clinically, it is an affordable treatment with potentially broad spectrum of applications in ophthalmology especially in the treatment of complex corneal disorders. The aim of this study was to evaluate the efficiency of autologous platelet‐rich plasma in the treatment of advanced pterygium and to compare it to conjunctival autograft technique.

Methods: A total of 26 patients (31 eyes) with advanced pterygium were included in this study. Mean BCVA was 0.7. Patients were divided into 2 groups according to the surgical technique used: PRGF group (16 eyes) and conjunctival autograft group (15 eyes). All patients underwent excision of pterygium followed by closure of the bare sclera either by PRGF or conjunctival autograft. Solid PRGF was either just placed on the corneal surface or sutured with 2 nodes of 10–00 nylon suture at conjunctiva. If necessary, the procedure was repeated. All patients had corneal OCT scan and photo before the treatment and during the follow up. Patients were followed at 2, 6, 12 and 18 months after the procedure.

Results: The mean surgery time was shorter in PRGF group (15.0 ± 2 min) compared to conjunctival autograft group (35.0 ± 5 min) (p = 0.001). Mean BCVA improved to 0.8 in both groups. The recurrence was observed in 2 eyes of conjunctival autograft group, while none of the eyes showed recurrence in PRGF group. Graft loss was observed in 2 cases in PRGF group and in 1 eye in conjunctival autograft group. None of the patients reported general or local side effects of the treatment.

Conclusions: PRGF is a simple, fast, reliable and effective therapeutic tool to promote wound healing and prevent recurrence after advance pterygium excision.
Plasmacytoid dendritic cell‐derived secretome ameliorates neuropathic corneal pain
Authors: Hamrah Pedram , Kenyon Brendan , Qiu Fangfang , Harris Deshea
Published: January 2024

Aims/Purpose: Prior work from our group has demonstrated a role for plasmacytoid dendritic cells (pDCs) in corneal nerve homeostasis. Herein, we sought to determine if pDC‐derived secretome could be used for the treatment of neuropathic corneal pain.

Methods: The BDCA2‐DTR transgenic mice, in which pDCs can be selectively depleted result in subsequent nerve degeneration, were utilized for ex vivo electrophysiology studies. Animals were treated with pDC secretome drops, beginning 1 day after initial depletion. Electrophysiologic recordings were taken at day 3 post‐depletion analysed. A ciliary nerve ligation model of neuropathic corneal pain (NCP), was used to assess the therapeutic potential of pDC secretome. Spontaneous and evoked pain responses were assessed by palpebral opening measurements and hyperosmolar saline, respectively.

Results: There was a significant reduction in cooling threshold following pDC depletion, which was rescued by pDC secretome treatment (26.85 ± 0.65°C vs. 29.52 ± 0.42°C; p < 0.05), restoring the cooling threshold to control levels (29.21 ± 0.51). Furthermore, nerve terminal exhaustion was reduced following pDC depletion and rescued by pDC secretome treatment (0.55 ± 0.08 vs. 1.11 ± 0.10; p < 0.01). Spontaneous pain responses were worse in the vehicle‐treated compared to pDC secretome‐treated group (0.67 ± 0.03 vs. 0.85 ± 0.02; p < 0.001). Similarly, evoked pain responses were worse in the vehicle‐treated compared to pDC secretome‐treated group (30.25 ± 1.50 wipes/30 sec vs. 15.38 ± 1.29; p < 0.0001).

Conclusions: Herein, we demonstrate that pDC secretome restores normal functioning of corneal cold receptors. Importantly, in a translational model of NCP, pDC secretome treatment improved both spontaneous and evoked pain responses. Thus, pDC secretome is a viable therapeutic modality for further development and may hold promise in treatment of NCP and other corneal nerve related diseases.

Reference

1. Jamali A, Kenyon B, Ortiz G, Abou‐Slaybi A, Sendra VG, Harris DL, Hamrah P. Plasmacytoid Dendritic Cells in the Eye. Prog Retin Eye Res 2021; 80: 100877.

2. Jamali A, Hu K, Sendra VG, Blanco T, Qazi Y, Zheng L, Turhan A, Hamrah P. Characterization of Resident Corneal Plasmacytoid Dendritic Cells and Their Pivotal Role in Herpes Simplex Keratitis. Cell Rep 2020; 32: 108099.
Polihexanide 0.8 mg/mL eyedrops as new treatment for severe Acanthamoeba keratitis
Authors: De Gregorio Chiara , Laborante Mariateresa , De Luca Andrea , Di Zazzo Antonio , Coassin Marco
Published: January 2024

Aims/Purpose: Novel effective medical therapy for Acanthamoeba Keratitis.

Methods: Interventional observational case series. Compassionate use of Polihexanide 0.8 mg/mL in 2 Acanthamoeba keratits (AK) patients. Two cases of diagnosed Acanthamoeba keratitis were unsuccessfully treated with Poliexamidine biguanide 0.02% and propamidine 0.1% applied hourly then tapered weekly. Clinical worsening was observed up to 4 weeks. Compassionate use of Polihexanide 0.8 mg/mL eyedrops was started.

Results: Corneal infection healed completely after 1 month in first case, and after 2 months of therapy in the second case. Corneal opacities and neovascularization decreased slowly, while BCVA (best corrected visual acuity) slightly and progressively increased per 3 months, and no infection recurred.

Conclusions: AK is a painful, long‐lasting (12 months) infection that drastically reduces a patient's quality of life. Polihexanide 0.8 mg/mL monotherapy lowers illness duration, chance of recurrence, and need for surgery in high risk settings, improving visual outcomes and quality of life.
Significative effect of COVID‐19 confinement on the evolution of myopia in children and young people in Spain
Authors: Recalde Sergio , Irigoyen Cristina , De la Puente Miriam , de la Viesca María Fraga , Gonzalez‐Zamora Jorge , Bilbao‐Malavé Valentina , Bezunartea Jaione , Hernandez Maria , de Viteri Manuel Saenz , Barrio Jesús , Fernandez‐Robredo Patricia , Layana Alfredo García
Published: January 2024

Aims/Purpose: The purpose of this study was to analyse whether the changes in habits during the pandemic confinement have resulted in a significantly greater increase in the dioptres (D) of children and young people compared to those of another year prior to the pandemic Confinement (PC). Moreover, CUVAF, as an objective measure of time spent outdoors, was also investigated in this cohort.

Methods: A retrospective observational study was carried out using three different cohorts of participants, one of children (9–17 years old), second one of young people (18–25 years old) and finally, adults (>25 years old) with some degree of myopia (<−0.75D). All of them with at least 3 annual graduation visits (two before March 2020 and one after June 2020). All participants underwent an automatic objective refraction, colour fundus photographs, and CUVAF area picture and measured the area with Fiji programme. All the participants filled out a questionnaire of life style and myopia history. For all statistical analyses, corrected p values <0.05 (two‐tailed) were considered statistically significant using Graphpad 8.0.1 Software.

Results: A total of 234 participants were recruited, 138 were children, 80 young people and 16 adults. The data showed that during the PC the 3 cohorts (children, youth and adults) decreased outdoor activities in similar high percentages (78%, 73% and 65% respectively) and similar indoor activities increased (80%, 83% and 75%). However, the children's graduation increased on average 0.51 D (SD ± 0.09) before PC and after PC increase 1.02 D (SD ± 0.11) with high significant increase (p < 0.0001). In the young, the increase was 0.33 D (SD 0.08) before PC and 0.61 (SD ± 0.09) after that (p > 0.01) and in adults it remained stable. There were no differences in the increase in D between children with and without CUVAF during PC, although those who had CUVAF started with lower gains (0.3 D) compared to those who did not (0.5 D) (p < 0.05).

Conclusions: The change in habits during the confinement of COVID‐19, with a drastic decrease in outdoor activities and an increase in indoor activities, has led to a significant increase in dioptres in young people and children, being much more pronounced in children. The CUVAF is a valid biomarker to measure the risk of myopia associated with outdoor activities.
Biofeedback fixation training as an important tool to supplement strabismic amblyopia treatment in aduls—preliminary results
Authors: Maneschg Otto Alexander , Barboni Mirella , Killik Petra , Bankó Éva Maria , Németh János , Nagy Zoltán Zsolt
Published: January 2024

Aims/Purpose: Fixation stability may be a biomarker of strabismus and amblyopia recurrence after strabismus surgery and therapeutic interventions to improve visual acuity in amblyopic eyes, respectively. We have recently shown that it is possible to improve fixation stability in adult amblyopic eyes after strabismus surgery using microperimetric biofeedback fixation training (BFT). In this study we evaluated the effects of BFT on fixation stability influencing monocular and binocular visual functions in adult patients with amblyopia.

Methods: Participants were 18 patients with monocular amblyopia (mean age = 35.2 ± 9.8 years; 6 females, 3 anisometropic, 5 strabismic and 10 mixed amblyopia). BFT has been applied monocularly to 13 amblyopic eyes either on the spontaneous preferential retinal locus (PRL) or to a fixation area close to the PRL. The other five subjects did not undergo BFT (control group). Best‐corrected visual acuity (BCVA near and distance), monocular (PRL) and dichoptic contrast sensitivity function (CSF) and fixation stability (BCEA 68%) were measured three times: baseline, after 10 and after 20 BFT sessions or twice within 6 months interval for the controls.

Results: Baseline fixation stability correlated positively with monocular amblyopic BCVA and CSF, especially in the high frequency range, whereas it was positively associated with dichoptic amblyopic CSF only in the low frequency range, most likely reflecting binocular imbalance. Preliminary results showed that BFT applied to amblyopic eyes improved fixation stability and visual functions. However, some clinical conditions may be required to achieve significant changes.

Conclusions: BFT applied to adult amblyopic eyes is a new potential approach to aid in the treatment of suppresive amblyopia in adult patients. Critical pre‐treatment fixational and/or sensorial criteria associated with satisfactory therapeutic effects of BFT on amblyopia remains to be investigated.
Visual function changes along the continuum of Alzheimer's disease
Authors: Elvira‐Hurtado Lorena , López‐Cuenca Inés , de Hoz Rosa , Salas Mario , Sánchez‐Puebla Lidia , Matamoros José A. , Fernández‐Albarral José A. , Salazar Juan Jose , Gil Pedro , Mestú Fernando , Ramirez Jose Manuel , Salobrar‐Garcia Elena
Published: January 2024

Aims/Purpose: The progression of Alzheimer's disease (AD) is manifested by a gradual transition from a preclinical phase, characterized by asymptomatic pathological alterations, to an advanced phase of AD accompanied by cognitive impairment. The aim of this study was to explore visual function along the entire AD continuum.

Methods: Each participant underwent a comprehensive visual examination, with only visually healthy individuals being selected for the study. The study comprised the following groups: controls (n = 53), positive family history of AD (FH+) (n = 13), mild cognitive impairment (MCI) (n = 23), mild AD (n = 25), and moderate AD (n = 21). The study analysed the results of visual acuity (VA) and contrast sensitivity (CS).

Results: A significant reduction in VA was identified between the control group and the MCI, mild AD and moderate AD groups. CS showed significant changes in all cognitive impairment groups compared to the control group and the FH+ group at spatial frequencies of 12 and 18 cpd. In contrast, significant differences were only observed at spatial frequencies of 3 and 6 cpd between the cognitively impaired groups, starting from moderate AD, with no detectable decrease in CS during the MCI phase. No differences were detected between the control group and the FH+ group. The tests showed a positive correlation with the Mini Mental State Examination score and exhibited a favourable predictive ability in the presence of memory impairment, with higher predictive performance observed in the advance stages of AD.

Conclusions: The presence of alterations in VA and CS can be observed as early as the MCI stage in individuals with AD. Recognizing the continuum of AD holds significant significance in early detection, with visual examination offering a straightforward and cost‐effective diagnostic tool for AD. Healthcare professionals can leverage this knowledge to gain a better understanding of the progressive nature of the disease.
The ganglion cell complex thickness and visual function in leber hereditary optic neuropathy
Authors: Hedström Johan , Nilsson Maria , Engvall Martin , Venkataraman Abinaya
Published: January 2024

Purpose: To evaluate the ganglion cell complex (GCC) thickness using the Iowa Reference Segmentation Algorithm in individuals with chronic Leber hereditary optic neuropathy (LHON) and to assess its relation to visual acuity, visual field sensitivity, and Estermann score.

Methods: In this study, a total of 17 patients (34 eyes) aged 16–72 with chronic LHON were enrolled. Visual acuity, visual fields, and Optic coherence tomography (OCT) were performed. Visual fields was evaluated with Estermann and a custom central 30‐degree test, both performed monocularly with the Octopus 900 Haag‐Streit Diagnostics. OCT imaging was performed using a Canon OCT HS‐100 to measure the retinal ganglion cell complex (GCC) thickness. The raw OCT images were exported to IOWA Reference Algorithm and the GCC segmentation was rechecked and manually recorrected if needed. The thickness obtained from the Iowa Reference Algorithms was analysed and compared against the automated segmentation provided by the OCT's inbuilt segmentation algorithm. The correlation between the GCC thickness from 9 ETDRS sectors and the visual function were analysed.

Results: On average the automated segmentation overestimated GCC thickness by 23.8 μm for all sectors. Macular central GCC correlated significantly with both visual field sensitivity and Estermann points missed (r = −0.486 and −0.396 respectively). Macular middle sector GCC thickness correlated significantly with visual acuity and visual field sensitivity (r = −0.586 and −0.396 respectively). GCC thickness in outer macular sector correlated significantly only with visual acuity (r = −0.471).

Conclusions: In patients with chronic LHON, GCC thickness in central and middle sectors of macula correlates well with the visual function. OCT imaging and precise ganglion cell thickness evaluations in the macula can provide useful information about the structural damage and level of visual impairment in chronic LHON patients.
Long‐term efficacy of idebenone in patients with Leber hereditary optic neuropathy in the LEROS study: Analysing change in visual acuity over time according to age at symptom onset
Authors: Llòria Xavier , Yu‐Wai‐Man Patrick , Carelli Valerio , Tomasso Livia , Klopstock Thomas
Published: January 2024

Aims/Purpose: Leber hereditary optic neuropathy (LHON) is a mitochondrial disease leading to progressive, bilateral vision loss. Childhood‐onset LHON has a relatively good prognosis, suggesting that age at onset influences disease progression and potential response to treatment. In LEROS, a Phase IV, open‐label interventional study (ClinicalTrials.gov NCT02774005), visual acuity (VA) outcomes following 24 months of idebenone treatment (IDE) were compared to those of a Natural History (NH) cohort.

Methods: LEROS included patients aged ≥12 years with a disease onset ≤5 years prior. Data from 181 patients were compared to retrospective data from a NH cohort (N = 372), matched by time since symptom onset. Here, we compare the difference in least squares‐mean VA change, or delta VA, from baseline to Month 24 in treated eyes versus those in the NH cohort (a negative value favours IDE). Eyes were stratified by time since symptom onset at baseline: subacute/dynamic (≤1 year) and chronic (>1 year) phase, and by age at symptom onset (<18 years, ≥18 years).

Results: In treated subacute/dynamic eyes from the <18 years group (n = 22 IDE), delta VA was +0.38 logMAR (p = 0.020) relative to the NH cohort (n = 22). In the chronic phase, delta VA was −0.08 logMAR (n = 16 IDE vs n = 37 NH eyes; p = 0.405). In subacute/dynamic eyes from the ≥18 years group, delta VA was −0.18 logMAR (n = 99 IDE vs n = 53 NH; p = 0.060). In the chronic phase, delta VA was −0.21 logMAR (n = 100 IDE vs n = 56 NH; p < 0.001).

Conclusions: In eyes of patients ≥18 years at symptom onset, VA improvement at Month 24 was greater in idebenone‐treated versus untreated NH eyes. Treatment benefit was particularly apparent in the chronic phase, corresponding to >10 additional letters on the ETDRS chart. In subacute/dynamic eyes, spontaneous VA recovery was unexpectedly high in the NH cohort. In chronic eyes from patients <18 years, a non‐significant trend favouring idebenone was observed.
The characterization of a new murine model of central areolar choroidal dystrophy showed that both cones and rods were affected by R195L mutation in peripherin‐2
Authors: Pastor María José Ruiz , Saez Xavier Sanchez , Kutsyr Oksana , Albertos‐Arranz Henar , Castillo Carla Sánchez , Ortuno‐Lizaran Isabel , Vidal Lorena , Martínez‐Gil Natalia , Maneu Victoria , Lax Pedro , Cuenca Nicolas
Published: January 2024

Aims/Purpose: Central areolar choroidal dystrophy (CACD) is a rare hereditary disease that leads to progressive retinal and choriocapillaris degeneration and vision loss. In Spain, there is a family suffering this disease, since they carry the mutation p.Arg195Leu in PRPH2. Our team have generated a mouse model of CACD carrying the same mutation as the Spanish patients. Our aim was to characterize the progression of CACD in the retina structurally and morphologically in this new murine model.

Methods: We studied the model C57BL/6J‐Prph2em1Sal by electroretinography, optomotor test, optical coherence tomography (OCT), immunofluorescence, confocal microscopy, and transmission electron microscopy (TEM) to assess the structural and morphological alteration of the retina during the progression of the disease in Prph2WT/WT, Prph2WT/KI, and Prph2KI/KI mice.

Results: A progressive retinal degeneration was found affecting the retina of both Prph2WT/KI and Prph2KI/KI mice models. We observed a significantly decreased retinal function from 3 months of age in Prph2KI/KI and 6 months of age in Prph2WT/KI, that was correlated with a progressive degeneration of the outer nuclear layer (ONL) shown by OCT images. The Prph2KI/KI mice showed a degeneration of photoreceptors with a reduction in the ONL thickness from 3 months of age, and a severe decrease in the number of photoreceptor rows at 6 months of age. The Prph2WT/KI, however, showed a slower decrease in the ONL thickness, starting from 6 months of age. Additionally, we found unstructured and shortened photoreceptor outer segments as evidenced by immunofluorescence against peripherin, rhodopsin and cone‐arrestin. Moreover, TEM images confirmed an abnormal stacking of photoreceptor discs.

Conclusions: The generated model is useful for the study of CACD. Moreover, the p.Arg195Leu mutation in PRPH2 causes the alteration of the outer segments first, triggering the degeneration of both cones and rods.