bluuebunny/crossref_metadata_2025 huggingface dataset:
Value of ophthalmological psychophysical test and MEG in subjects at high risk for sporadic Alzheimer's disease
Authors: López‐Cuenca Inés , Salobrar‐Garcia Elena , Sanchez‐Puebla Lidia , de Hoz Rosa , Nebreda Alberto , García‐Colomo Alejandra , Bruña Ricardo , Ramírez‐Toraño Federico , Barabash Ana , Gil Pedro , Mestú Fernando , Ramirez Jose Manuel , Ramirez Ana Isabel , Salazar Juan Jose
Published: December 2022

Purpose: The aim of this work was to analyse in subjects at high risk of developing Alzheimer's disease (AD) the possible correlation between psychophysical tests and magnetoencephalography (MEG) in comparison with control subjects.

Methods: Extensive ophthalmological analysis, MEG recording, genotyping and magnetic resonance imaging (MRI) were performed on 149 healthy subjects, of whom 109 had a family history of the disease and 40 did not. This sample was subdivided into subgroups aged 40–60 years with an increased risk of AD based on the presence of the ApoEɛ4 allele (ApoEɛ4+) and family history (FH+). 28 participants as higher risk group (ApoEɛ4+ and FH+) and 16 participants as lower risk group (FH‐ and ApoEɛ4‐).

Results: In the ApoEɛ4+ and FH+ group, a significant increase in visual acuity was observed, as well as an increase in some spatial frequencies of contrast sensitivity. In addition, in this group, some areas of the inner plexiform layer and the inner nuclear layer were thinned. Between the risk groups, when directly comparing M100 latency or temporal frequency activity associated with the visual response, no significant differences were found. However, there was an association between higher visual acuity and earlier M100 latency and increased activity in the high‐risk groups.

Conclusions: There seems to exist an early hyperactivation of the visual system, which would act as a compensatory mechanism, or be a manifestation of a biological malfunction that ultimately leads to toxicity. This hyperactivation represents the first evidence of the consequences of early retinal damage, associated with genetic risk, on visual processing. These changes observed by readily available and non‐invasive techniques could constitute a set of biomarkers for early detection of the disease and assessment of the efficacy of possible future treatments.
3D printed enucleated eye holder for research and surgical training
Authors: Yang Yunfang , Zhang Yunlan , You Zhong , Ching Jared
Published: December 2022

Purpose: The aim of this study is to provide an affordable eye holder to secure enucleated eyes for the purposes of ophthalmology surgical training or research. Whilst mannequin heads are an excellent tool for surgical training, a surgical microscope is pre‐requisite to accommodate this. Table top microscopes are widely available and commonly used for both research and surgical training, however, there are a limited number of available products to secure the eye reliably in this setting. We present a 3D‐printed enucleated eye cup holder that can be mass produced as a low‐cost training tool.

Methods: Using Solidworks, we designed a 3D printable modular device that consists of three pieces forming an eye cup holder. The main cup has 8 symmetric round holes to secure the eye in the horizontal and vertical planes either on recti muscles, their insertions, conjunctiva or episclera using sutures. This provides a customizable level of stability to allow precise surgery that can be made more repeatable for research purposes and surgical training. Two support pillars mount the main cup on an optical board which is placed under the microscope. The main cup can be reprinted for replacement conveniently and can be customised to adapt to different microscope dimensions and different cadaveric eyes.

Results: This system has been tested on cadaveric porcine and human eyes in both training and research environments. During the operation, the main cup is placed on the base of the microscope and mounted on the optical board underneath by support pillars. The whole system is fixed on optical board to achieve better stability as well as adaptability to different microscopes. Other equipment can be added on the optical board for further tests. The eyes are sutured securely on the holder and the position is adjustable. Ophthalmologists and trainees were able to practice appropriately on the system. This system was affordable at a cost of approximately €24 to print.Conclusions: Herein, we present a 3D‐printed enucleated eye cup holder that can be secured to the base of a microscope using an optical board. The adjustable positioning of the eye via suturing provides a convenient surgical training and research experience. The holder is released as an open‐source computer‐aided design file with customizable dimensions for interested trainees and researchers.

image
Comparative evaluation of corneal characteristics in eyes of primary congenital glaucoma and Axenfeld‐Rieger syndrome
Authors: Mahalingam Karthikeyan , Nathiya Venkatesh , Singh Abhishek , Nag T. C. , Sen Seema , Titiyal Jeewan , Gupta Viney , Gupta Shikha
Published: December 2022

Purpose: To evaluate and compare the primary dysgenesis of cornea in Primary Congenital Glaucoma (PCG) and Axenfeld‐Rieger Syndrome (ARS).

Methods: 26 eyes of PCG and 40 eyes of ARS were included. The following parameters were noted: clinico‐demographic profile; ASOCT of cornea/angle; Ocular biomechanical parameters, intraocular pressure (IOP) and central corneal thickness(CCT) (using Corvis ST); corneal aberration (iTrace, Tracey Technologies); morphological and cellular structure of the cornea (Confoscan HRT‐III:RCM) and histopathology of cornea (after keratoplasty).

Results: Mean corneal diameter of PCG (13.4 ± 1 mm) was higher (p = 0.01) than ARS (11.7 ± 1.6 mm). Haab striae were observed more in the eyes of PCG (63.6%) than ARS (5%). Posterior corneal hyperreflectivity was present in 100% PCG eyes v/s 85.2% ARS (p = 0.006). Angle dysgenesis was comparable: PCG (85.4%) and ARS (90.7%). The presence of a double membrane sign, indicating thickened PDL and DM, was visible exclusively in eyes of PCG (29.2%) v/s singular posterior corneal hyperreflectivity (85.2%), indicating thickened DM complex, visible in eyes of ARS. Corneas of ARS were 52.3 μm thicker than PCG. In eyes of both PCG and ARS, the most common total ocular aberration was astigmatism. The endothelial cell count in PCG {1703 ± 661 cells/mm2} and ARS {1442 ± 397 cells/mm2} was comparable. The PDL thickness in the eyes of PCG (11.8 μm) was greater than ARS (9.1 μm). In immunohistochemistry, all tissues of PCG (n = 9) were collagen IV positive (indicating presence of PDL), two tissues of ARS (22.2%) were collagen IV negative.

Conclusions: The difference in characteristic of PDL may cause difference in corneal enlargement and angle differences between the two groups.
Ophthalmic liposomal formulations using synthetic phospholipids for the treatment of dry eye disease
Authors: Casamayor Miriam González‐Cela , Cano José Javier López , Andrés‐Guerrero Vanessa , de la Torre Marta Vicario , del Castillo José Manuel Benítez , Vanrell Rocío Herrero , Molina‐Martínez Irene T.
Published: December 2022

Purpose: Liposomes composed of soy phosphatidylcholine (PC) have been widely used in artificial tears for the treatment of dry eye disease (DED) due to their ability to supplement the lipid layer of the ocular surface. The disadvantage of PC extracted from natural sources is the difficulty of standardizing its fatty acid composition. Therefore, the use of synthetic phospholipids such as 1,2‐dioleoyl‐sn‐glycero‐3‐phosphocholine (DOPC) and Dimyristoylphosphatidylcholine (DMPC) allows better characterization and standardization than those from natural sources, being of interest in the preparation of ophthalmic liposomal formulations for DED.

Methods: Liposomal formulations comprised of DOPC (F1) and DOPC combined with DMPC (F2) were prepared according to the Bangham technique and dispersed in a borate‐trehalose buffer. Formulations were characterized in terms of pH, size, osmolarity and surface tension. In vitro tolerance was performed in human corneal epithelial cells and compared with soy PC liposomal formulation.

Results: Both F1 and F2 synthetic liposomal formulations showed suitable properties for topical ophthalmic administration for DED such as hypotonicity (F1: 244.8 ± 0.74; F2: 252.5 ± 0.08 mOsm/L), neutral pH (F1: 7.52 ± 0.01; F2: 7.54 ± 0.02), low surface tension (F1: 24.53 ± 0.70; F2: 26.93 ± 0.49 mN/m) and a vesicle size of 150.8 ± 59.60 and 181.00 ± 49.83 nm for F1 and F2 respectively. Synthetic phospholipids outperformed soy PC liposomes regarding in vitro tolerance in a very sensitive corneal line, exhibiting cell viability values after 1 hour exposure of 88.71 ± 7.32% and 82.36 ± 8.84% for F1 and F2 respectively compared to soy PC liposomes (73.08 ± 8.74%). After simulated chronic exposure (4 h), cell viability of F1 (78.26 ± 1.65%) and F2 (79.08 ± 1.75%) were higher than the one obtained for PC liposomal formulation (64.53 ± 6.73%).

Conclusions: Liposomes composed of synthetic phospholipids are potential candidates for the development of artificial tears for DED treatment.
Synchrotron radiation‐based infrared micro‐spectroscopy characterization of different types of epiretinal proliferations
Authors: Andjelic Sofija , Kreuzer Martin , Hawlina Marko , Lumi Xhevat
Published: December 2022

Purpose: To assess epiretinal proliferations bio‐macromolecules and to provide their molecular fingerprint for better understanding of epiretinal proliferations, we used synchrotron radiation‐based Fourier transform infrared (SR‐FTIR) micro‐spectroscopy.

Methods: The membranes were collected from routine pars plana vitrectomy. The biochemical differences between idiopathic nonvascular epiretinal membranes (ERMi), membranes in proliferative vitreoretinopathy (PVRm) and neovascular membranes in proliferative diabetic retinopathy (PDRm) were evaluated and compared by using SR‐FTIR micro‐spectroscopy at the MIRAS beamline of the ALBA Synchrotron, Barcelona, Spain and multivariate analysis.

Results: PVRm differs the most from ERMi and PDRm in all spectral regions. We demonstrated the presence of silicone oil (SO) or polydimethylsiloxane (PDMS) in the structure of PVRm membrane after SO endotamponade suggesting that SO, in addition to many benefits as an important tool in vitreoretinal surgery, can also contribute in PVRm formation. We also showed the differences between PVRm, PDRm and ERMi in protein and lipid structure, collagen content and maturity.

Conclusions: Our results obtained by SR‐FTIR increase the knowledge about the total proteins, lipids and nucleic acids in different epiretinal proliferations while offering also the evidence that SR‐FTIR is sensitive to the pathologic processes of epiretinal proliferations. We emphasize the different macro‐molecular composition of three different types of epiretinal proliferation stemming from different components and metabolic processes taking place as well as the caution needed when using SO in vitreoretinal surgery.
Outcomes of newly referred patients with suspected angle closure: Do we need to redefine the clinical pathways?
Authors: Narayan Akshay , Nolan Winnie , Raja Aneela , Nathwani Neil , Tur Sergio Bordajandi , Thomas Rachel , Scott Andrew , Martins Alessandra , Founti Panayiota
Published: December 2022

Purpose: To investigate outcomes of referrals for suspected angle closure and to explore whether anterior segment optical coherence tomography (AS‐OCT) can be used to tighten triaging criteria in a glaucoma virtual clinic.

Methods: Retrospectively collected data. The first audit (04/2018–03/2019) identified referrals for suspected angle closure in the absence of other glaucoma‐related findings (primary angle closure suspect (PACS) referrals). All patients underwent gonioscopy. The second audit (04‐08/2019) identified consecutive patients with suspected angle closure in a virtual clinic. Management outcomes were assessed, using gonioscopy as the reference standard. Outcomes were re‐audited after changing the triaging criterion from angle width < 10° to iridotrabecular contact (ITC) in ≥1 quadrants on AS‐OCT.

Results: Out of 1754 glaucoma referrals (first audit), 24.6% (431/1754) were PACS referrals. Of these, only 10.7% (42/393) had an occludable angle on gonioscopy, with 97.6% (41/42) being PACS. Of these, 78% (32/41) underwent laser peripheral iridotomy. Out of 137 referrals in the virtual clinic (second audit), 66.4% (91/137) were triaged to the face‐to‐face clinic. Of these, 31.9% (29/91) were discharged. AS‐OCT had positive and negative predictive value of 74.3% (95% confidence intervals (CI) 57.8–86.0) and 82.1% (95% CI 70.0%–90.2%), respectively, in detecting ITC in ≥1 quadrants. In the re‐audit 45.9% (45/98) of those with suspected angle closure were triaged for gonioscopy, with 24.4% (11/45) of them being discharged.

Conclusions: PACS referrals represent a substantial burden to hospital‐based services and their ‘accuracy’ appears to be low. ITC in ≥1 quadrants on AS‐OCT can be useful in triaging those who need further evaluation with gonioscopy.
Acute omega‐3 fatty acid supplementation confers novel neurovascular‐protective effects on the retinal and ophthalmic arterial proteome of Cyp2c44−/− mice
Authors: Manicam Caroline , Herfurth Anna , Grus Franz , Pfeiffer Norbert , Perumal Natarajan
Published: December 2022

Purpose: Cytochrome P450 (CYP) gene mutations are associated with the pathogenesis of glaucoma. Although the molecular mechanisms are largely unknown, omega‐3 polyunsaturated fatty acids (ω3) and the CYP‐derived lipid mediators play significant roles in the neurovascular functions of ocular vascular beds. This study explored the proteome changes attributed to inherent lack of the main murine CYP gene (Cyp2c44) and the effects of acute dietary supplementation with ω3 in the retina (R) and ophthalmic artery (OA) in vivo.

Methods: Male mice with targeted deletion of the Cyp2c44 gene (KO) and their floxed littermates (WT) were gavaged daily for 7 days with 0.01 ml/g ω3 composed of menhaden fish oil. Another group in respective strains served as vehicle‐treated controls. R and OA were isolated at day 8 post‐treatment (n = 9/group) and subjected to mass spectrometry (MS)‐based proteomics and in‐silico bioinformatics analyses.

Results: Acute ω3 administration elicited significant differential expressions of 56 and 18 proteins in the R and OA, respectively. The KO mice exhibited significant retinal degeneration (p = 1.82 E‐2) and compromised microtubule dynamics (p = 9.46 E‐3), while mitochondrial chain deficiency (p = 3.77 E‐8) and inhibition of molecular transport (p = 5.24 E‐5) were implicated in OA. Remarkably, ω3 supplementation in KO mice resulted in significant changes in the R proteins involved in vision functions, and heightened metabolic activity via glycolysis and AMPK signalling (CRYBB2, ALDOC, ENO2). Noteworthy, ω‐3 had a profound influence on the regulation of OA proteins involved in the inhibition of necrosis, activation of molecular transport and intercellular junctional organization (HSPA8, HK1, YWHAB).

Conclusions: In gist, short‐term dietary supplementation with ω3 confers physiologically relevant beneficial effects on the ocular vascular beds via specific neuro‐vasculoprotective signalling mechanisms in the absence of Cyp2c44. The potential adjunct use of ω3 for glaucoma therapy needs further investigation.
Preliminary results of serial sessions of a newly developed at home device using low‐level light therapy for the treatment of dry eye disease
Authors: Scalzo Giovanna Carnovale , Vaccaro Sabrina , Borselli Massimiliano , Scorcia Vincenzo , Giannaccare Giuseppe
Published: December 2022

Purpose: To evaluate objective parameters of ocular surface and ocular discomfort symptoms after the use of a new at‐home device in patients with dry eye disease (DED) owing to meibomian gland dysfunction (MGD).

Methods: In this prospective study patients with mild to moderate DED owing to MGD not successfully responding to first‐line therapy (tear substitutes and eye lid hygiene) were recruited. Non‐invasive ocular surface examination was carried out by means of Keratograph 5 M (Oculus, Wetzlar, Germany) for the evaluation of: (i) tear meniscus height (TMH); (ii) non‐invasive break‐up time (NIBUT); (iii) ocular redness; (iv) meibomian gland loss (MGL). Ocular Surface Disease Index (OSDI) questionnaire was used to assess ocular discomfort symptoms. Patients were evaluated before (T0) and after 1 week of treatment consisting of 4 serial sessions (every other day) of low‐level light therapy (LLLT) with a newly‐developed at home device.

Results: Seven patients (6 females and 1 male, mean age 56.86 ± 7.29 years) were enrolled and completed regularly the entire cycle of 4 home sessions without any adverse event. Mean value of NIBUT increased significantly at T1 compared to T0 (respectively 5.81 ± 2 0.85 vs. 7.64 ± 3.93 s; p = 0.035); conversely, there were not statistically significant differences for TMH, redness score and MGL. In addition, OSDI score improved at T1 compared to T0 (respectively, 20.17 ± 9.5 vs. 31.14 ± 9.83; p < 0.001).

Conclusions: One week of serial sessions of a newly‐developed at home device using LLLT improved significantly tear stability and subjective discomfort symptoms in patients with DED owing to MGD. This strategy could represent a new therapeutic option in the armamentarium of MGD treatments.
Uveal effusion after trabeculectomy: Management challenges
Authors: Cheour Monia , Nouri Slim , Abid Yosra , Sassi Hela , Meriem Ouederni
Published: December 2022

Purpose: To discuss the causes and risk factors of uveal effusion after trabeculectomy and to describe the management of this complication.

Methods: This observational retrospective case series included 5 consecutive cases of uveal effusion that developed after trabeculectomy with intraoperative 5‐FU. All patients underwent ophthalmological examination including best corrected visual acuity (BCVA) measurement, anterior segment and fundus examinations. Fundus photography, B‐scan ultrasonography and Swept Source optical coherence tomography (SS‐OCT) were used to detect and monitor choroidal detachment and hypotony maculopathy. Anterior segment optical coherence tomography (AS‐OCT) was performed to assess iridocorneal angle opening and anterior chamber depth.

Results: Four men and one woman were included. Mean age was 48.8 ± 15.1 y. One patient had nanophtalmia confirmed by B‐scan ultrasonography while four patients had postoperative hypotonia caused by overfiltration (3 cases) and bleb leak (1 case). All patients received corticosteroids and cycloplegics associated with a reformation of the anterior chamber and in one case we performed bleb revision. We showed resolution of the choroidal effusion, normalization of the ocular hypertension and restoration of visual acuity in all cases.

Conclusions: Uveal effusion after trabeculectomy occurs in 3%–34% of cases. Its management can be challenging and requires close monitoring. Conservative management can overcome choroidal detachment, restore visual acuity and avoid aggressive surgery.

References.

1. Schrieber C, Liu Y. Choroidal effusions after glaucoma surgery. Current Opinion in Ophthalmology. 2015; 26(2): 134–42.

2. Senthikumar VA, Michra C. Ultra‐widefield image of choroidal detachment after combined glaucoma filtration surgery. Indian J Ophthalmol. 2020; 68(8): 1669.
Implementation of a virtual screening service for hydroxychloroquine and chloroquine retinopathy: One‐year results
Authors: Ferreira Catarina , Fernandes Joana , Saraiva Eduardo , Fonseca Sofia
Published: December 2022

Purpose: To evaluate the results of a new virtual screening service for hydroxychloroquine (HQC) and chloroquine (CQ) retinopathy.

Methods: Prospective study including patients under long‐term HCQ or CQ therapy referred for screening at a single ophthalmic centre in Portugal over a one‐year period. The virtual clinic consisted of a visit for functional and structural testing, in accordance with the guidelines on HCQ retinopathy screening1,2, followed by a later review by an experienced consultant. Individualized counselling for both patients and prescribing physicians was provided on retinal toxicity risk, safe dosing, and adequate screening intervals.

Results: A total of 93 patients under treatment with HCQ attended the virtual clinic. Systemic lupus erythematosus (38.7%) and rheumatoid arthritis (18.3%) were the most prevalent diagnoses. Mean daily HCQ dosing was 5.2 ± 1.6 mg/Kg, with 46.2% patients using a daily dose greater than 5 mg/Kg. Median treatment duration was 48 months (range: 1–264) and 49.5% patients had been treated for longer than 5 years. Renal disease was present in 11 patients (11.8%) and 7 (7.5%) had pre‐existing retinal conditions. Structural changes in macular optical coherence tomography and fundus autofluorescence were rarely detected (3.3%). In contrast, 16 patients (17.2%) presented with abnormal 10‐2 visual field testing. Multifocal electroretinogram was performed in 14 patients (15.1%), detecting characteristic abnormalities of drug toxicity in one patient, with a definite diagnosis of severe HCQ retinopathy. Recommendation for dose adjustment was given in 47.3% of cases, including advice to discontinue HCQ use in 7 (7.5%) patients based on risk factors.

Conclusions: Retinal toxicity is a rare adverse effect of HCQ, a therapy increasingly used in the management of autoimmune disorders. Virtual clinics could be a safe and sustainable care delivery system for adequate counselling, risk assessment and early retinopathy detection.

References.

1. Marmor MF, et al. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 revision). Ophthalmology 2016; 123:1386–1394.

2. Royal College of Ophthalmologists. Hydroxychloroquine and chloroquine retinopathy: recommendations on monitoring. London: Royal College of Ophthalmologists, 2020.
Pathogenic variant c.61G > C in NLRP3 lowers NLRP3 inflammasome activation threshold in patients with keratitis Fugax Hereditaria
Authors: Kawan Sabita , Backlund Michael , Immonen Annamari , Kivelä Tero , Turunen Joni
Published: December 2022

Purpose: To elucidate the effect of NLRP3 variant c.61G > C on interleukin‐1β (IL‐1β) secretion in keratitis fugax hereditaria (KFH), a cryopyrin‐associated periodic syndrome limited to the eye, and to probe the potential modifying role of prednisolone.

Methods: Peripheral blood mononuclear cells (PBMCs) isolated from whole blood of patients with KFH and healthy controls were grown under steady‐state conditions or primed with lipopolysaccharide (LPS) with or without prednisolone, and subsequently activated with adenosine triphosphate (ATP). Cell lysates and proteins precipitated from the cell culture media were separated by SDS‐PAGE. NLRP3, procaspase‐1, and IL‐1β were visualized by western blotting. The concentration of secreted IL‐1β in the culture media was quantified by ELISA.

Results: A lower threshold for IL‐1β secretion following priming of the NLRP3 inflammasome with LPS was observed in patients‐derived PBMCs, compared to healthy controls (median, 124 vs. 16 pg/ml respectively). Interestingly, in PBMCs derived from patients with frequent KFH symptoms, LPS priming alone was able to trigger substantial IL‐1β secretion (median, 522 pg/ml), whereas those of patients experiencing occasional KFH attacks showed a subtler release of IL‐1β (median, 85 pg/ml). LPS and ATP treated PBMCs from patients with KFH showed significantly diminished IL‐1β secretion with prednisolone treatment (p = 0.04). NLRP3 expression was significantly enhanced with LPS stimulation (p = 0.03) whereas procaspase‐1 expression was not affected.

Conclusions: PBMCs from patients with KFH are more prone to secrete IL‐1β, confirming the presumption that the c.61G > C is a gain‐of‐function variant. Furthermore, prednisolone is confirmed as a potent drug to reduce IL‐1β secretion in KFH.
MR‐based follow‐up after brachytherapy and proton beam therapy in uveal melanoma
Authors: Tang Michael , Ferreira Teresa , Jaarsma‐Coes Myriam , Klaassen Lisa , Marinkovic Marina , Vu Khanh , Rasch Coen , Creutzberg Carien , Horeweg Nanda , Klaver Yvonne , Rodrigues Myra , Luyten Gregorius , Beenakker Jan‐Willem
Published: December 2022

Purpose: Comparison of Magnetic Resonance Imaging (MRI) with conventional ultrasound for the follow‐up in Uveal Melanoma (UM) patients treated with brachytherapy or proton beam therapy (PBT).

Methods: 26 UM patients were scanned before, 3, 6 and 12 months after ruthenium brachytherapy (n = 13) or PBT (n = 13) at 3Tesla MRI. Tumour prominence measurements were compared between MRI and ultrasound. On Perfusion weighted MR‐imaging (PWI), the relative enhancement and outflow at 2 min after peak were assessed. Treatment response was defined as a reduction of ≥0.6 mm prominence and/or ≥5% perfusion outflow was achieved.

Results: Pretreatment prominences were comparable on MR and ultrasound (mean absolute difference 0.49 ± 0.46 mm), larger differences were observed at 3 and 6 months post treatment (0.88 ± 0.86 mm and 0.74 ± 0.72 mm, respectively). At 12 months post treatment, the difference was reduced to 0.55 ± 0.33 mm. Pretreatment, 76% of the UM showed a washout perfusion curve. The pretreatment average enhancement and outflow were 98% (SD:49%) and 31% (SD: 25%) respectively. At 3 months post treatment tumours showed 41% less outflow on average with more favourable perfusion curves (e.g. 68% showed a persistent or plateau curve). At 6 and 12 months post treatment, tumours continued to show less outflow (respectively, −47% and −38%) and more favourable perfusion curves (respectively, 79% and 76% with either persistent or plateau curves). These, generally favourable, perfusion changes were also observed when no reduction in prominence was yet apparent, which is why treatment response was more frequently detected on MRI as opposed to ultrasound. For example, at 3 months post treatment >80% of patients were already detected on MRI versus 46% on ultrasound.

Conclusions: MRI is beneficial for the follow‐up of UM patients, especially for PBT treated patients as these generally take longer before a reduction in prominence can be observed.
Comparison of ocular aberrations and retinal image quality provided by a validated aberrometer and a new open field aberrometer for VEMoS project
Authors: Alio Jorge , Martínez‐Abad Antonio , José‐Martínez Marina , Mira‐López Paula
Published: December 2022

Purpose: The aim of this observational study was to compare the retinal image quality and ocular aberrations provided by a validated aberrometer and by a new open field aberrometer.

Methods: This is an observational and comparative study composed by healthy eyes not presenting cataract or ocular pathologies affecting media transparence or visual function. Patients underwent a measurement of ocular aberrations by a closed field aberrometer (Osiris, CSO) and by an open field aberrometer developed for VEMoS European project (OFA, CSO). Both measurements were performed by a qualified optometrist and the pupil size selected for the analysis was 4 mm. SPSS program was applied for the statistical analysis, particularly Wilcoxon test was used to compare both devices considering a significance of 0.05.

Results: The study included 20 eyes of 20 patients with a mean age of 36.2 ± 9.7 years. The sphere was significantly more negative with Osiris in comparison with OFA (−0.33 ± 2.17 diopters vs. 0.29 ± 2.17 diopters, p < 0.001), the spherical aberration was also slightly lower with Osiris (0.02 ± 0.03 microns vs. 0.03 ± 0.03 microns, p: 0.045). The rest of aberrometric coefficients including the cylinder, coma, trefoil, quadrefoil and secondary astigmatism showed no significant differences between devices (p > 0.05). Moreover, the point spread function did not presented statistical differences, but a trend to obtain higher values was observed in Osiris (0.219 ± 0.127 vs. 0.189 ± 0.126, p: 0.370).

Conclusions: The sphere provided by an open field aberrometer was significantly more positive comparing with a close field aberrometer probably associated to an accommodative response induced in close field aberrometers. Similarly, the spherical aberration assumed small changes between devices, which would be generated also by accommodation. The rest of parameters showed no differences between devices indicating a suitable agreement between devices for these coefficients.
Macrophage infiltration in the cornea in a mouse model of sepsis
Authors: Quirce Susana , Ramírez Kristy Tatiana Rodríguez , Vidal‐Sanz Manuel , Agudo‐Barriuso Marta
Published: December 2022

Purpose: To analyse the effect of a systemic inflammatory insult induced by lipopolysaccharide (LPS) administration on the cornea in mice.

Methods: Male and female C57BL/6J mice were injected with a single intraperitoneal injection of LPS (5 mg/kg). Intact animals were used as control. At 21 days after LPS administration animals were sacrificed with sodium pentobarbital. Corneas were dissected as flat mounts or histological sections (16 μM) and Iba1 (microglia and macrophages) and CD45 (activated microglia and macrophages) immunodetected.

Results: In LPS treated animals but not in intact ones, microglia/macrophages were found in all corneal layers while in corneal flat mounts Iba1 + Cd45+ cells were observed through the corneal surface with higher density in the periphery.

Conclusions: Sepsis causes infiltration and activation of microglia/ macrophages in the murine cornea that lasts up to 21 days.
Association of visual acuity and vessel density in glaucoma patients with myopia
Authors: Kim Seong Ah. , Park Chan Kee , Park Hae‐Young Lopilly
Published: December 2022

Purpose: To evaluate correlation between vessel density (VD) and visual acuity (VA) in glaucoma patients with myopia.

Methods: 65 eyes of 70 open angle glaucoma patients with myopia were included in this study. Myopia was defined as axial length > 26.0 mm. Decreased VA was defined as <20/25. Visual field (VF) 24‐2 and 10‐2 were both performed. Superficial and deep peripapillary VD (PPVD) were evaluated using radial peripapillary capillary VD and choriocapillary VD in peripapillary atrophy (PPA), respectively, of optical coherence tomography angiography (OCT‐A). Temporal and nasal superficial PPVD around optic nerve head (ONH), and the ratio of temporal to nasal PPVD were evaluated. Macular VD was evaluated using superficial and deep layer of OCT‐A. PPA with and without gamma‐zone PPA, disc torsion, and disc‐fovea distance (DFD) were evaluated.

Results: 32 eyes of normal VA and 33 eyes of decreased VA were enrolled. In logistic regression analysis, thinner ganglion cell complex (GCC) (p = 0.005), lower deep PPVD (p = 0.028), and longer DFD (p = 0.049) were significantly associated with decreased VA. Worse VA was significantly associated with older age (p = 0.005), thinner GCC (p < 0.001), more decreased ratio of temporal to nasal superficial PPVD (p = 0.022), and lower deep PPVD (p < 0.001) in linear regression analysis. Worse mean deviation of VF10‐2 was significantly correlated with thinner GCC, lower temporal PPVD, and lower deep PPVD, respectively in linear regression analysis (all p < 0.001).

Conclusions: Eyes with decreased VA showed lower temporal superficial PPVD, deep PPVD, and thinner GCC in patients with myopia. Decreased VA was also associated with longer DFD. Decreased VD that may be affected by scleral deformation at temporal to ONH was associated with central scotoma and decreased VA.
Quantification of vascular pathology in the retina through probability distributions of central artery and vein width equivalent
Authors: El Youssfi Asmae Igalla , Cedrun‐Sanchez Juan , Puell María , Alonso José Manuel López
Published: December 2022

Purpose: A semi‐automated method of measuring the Central Retinal Artery Equivalent (CRAE) and Central Retinal Vein Equivalent (CRVE) has been developed. The method was used to calculate parametric probability distribution for CRAE and CRVE in healthy retinas in order to quantify possible vascular pathology degree.

Methods: Using the ARIA software (MATLAB), the diameters of the retinal vessels located in a ring with radii 0.5 and 1 diameter of the optic disc were quantified. A measurement of CRAE and CRVE was obtained for two data base of healthy retinas (15 and 52 patients) measured with different retinal cameras. Subsequently, the probability distribution of CRAE and CRVE was calculated, as well as the bootstrap estimators of the mean, standard deviation, skewness, and kurtosis. MATLAB functions were used to select the parametric distribution that best fits the data. The Mahalanobis distance of each retina to healthy distribution was obtained. This classification distance was applied to healthy and glaucoma retinas.

Results: The fits to theoretical distributions were good for a Generalized Extreme Value Distribution (gev) characterized by three parameters (scale, mean and standard deviation). They appear to be consistent across different databases. In retinas with glaucoma, the Mahalanobis distance allows the degree of pathology to be quantified. Moreover, the method can be used to classify the healthy retinas.

Conclusions: The possible existence of parametric probability distributions for values of vascular calibres opens the possibility of quantifying the degree of vascular pathology.
Snail track a in a case with anterior segment dysgenesis caused by a novel FOXC1 variant
Authors: Jedličková Jana , Skalická Pavlína , Dudakova Lubica , Liskova Petra
Published: December 2022

Purpose: To identify disease‐causing mutation in one proband of Czech origin with anterior segment dysgenesis (ASD) and to describe the associated phenotype.

Methods: After complex ophthalmic examination of 15‐year‐old female at the Department of Ophthalmology, 1st Faculty of Medicine, Charles University and General University Hospital in Prague, DNA extraction from blood was performed. Pathogenic variants in genes associated with ASD were searched using exome sequencing. Confirmation of the presence of causal variant and segregation within the family members was performed by Sanger sequencing. Standard paternity testing was performed to confirm de novo origin of the variant.

Results: Except for common finding of ASD as mild iris hypoplasia, pupil deformation in both eyes, and unilateral iridocorneal adhesions, there was a snail track lesion of the right cornea at the level of the Descemet membrane. Molecular genetic analysis revealed that the proband was a carrier of a novel heterozygous frameshifting variant in the FOXC1 gene: NM_001453.3: c.605del, p.(Pro202Argfs*113). De novo origin was confirmed by the absence of the variant in healthy parents and sister of proband, and further by the paternity testing.

Conclusions: Loss of visual functions in ASD is often very acute, therefore establishing molecular diagnosis highly impacts patient management and enabling prenatal diagnostics. Further studies need to be performed to verify if there is a true association of snail tracks and pathogenic variants in FOXC1.
Validation of a novel software‐based platform to extract oculometric measures
Authors: Rosset Israel , Raveh Eitan , Shimon Assaf Ben , Anisimov Vova , Ben‐Ami Edmund , Kreitman Rivka , Breakstone Micha
Published: December 2022

Purpose: Eye‐tracking systems are a valuable tool in the assessment of disorders by detecting eye movement abnormalities. However, current systems require lab settings, extraction of oculometric measures entails dedicated long sessions, and operation requires qualified personnel. Recently, a novel software‐based platform was developed, using a webcam, enabling the extraction of oculometric measures in a short test with seamless operation. The aim of this study was to validate this platform as compared with a validated eye‐tracker.

Methods: 82 participants (51 females, age range 21–88) were evaluated with a software‐based platform (NeuraLight, Israel) in a 15‐minute eye‐tracking test. Participants were presented with different stimuli for various tasks. During the test, data from a validated eye‐tracker (Tobii Pro, Sweden) were captured. Correlations between oculometric measures captured by both methods were calculated using Pearson correlation. Observable information on demographic data was measured using Fisher information matrix.

Results: Eye and gaze positions captured by the NeuraLight platform were highly correlated with eye‐tracker (r = 0.9–0.99, p < 0.01). Saccade and anti‐saccade latency, pro‐saccade and anti‐saccade error rates, position and velocity gain for all tasks were all highly correlated (r > 0.9, p < 0.01). Relative root mean square error of all measures in both methods was <0.1. Saccadic latency and fixation time were found to be in relation with participants' age.

Conclusions: NeuraLight platform was significantly correlated with a validated eye‐tracker, providing high accuracy for eye and gaze positions and oculometric measures. Relation between oculometric measures and age was established. The platform can be implemented for assessment of eye movements in practice. Future studies are needed to use the platform in various conditions.
Long‐term efficacy and safety of idebenone in patients with Leber's hereditary optic neuropathy (LHON) in the subacute/dynamic phase: Results from the prospective, natural history‐controlled LEROS study
Authors: Yu‐Wai‐Man Patrick , Carelli Valerio , Tomasso Livia , Klopstock Thomas ,   the LEROS Study Group
Published: December 2022

Purpose: Idebenone is approved in Europe for the treatment of LHON – a rare mitochondrial disorder resulting in severe, bilateral vision loss. Controlled data beyond a 6‐month treatment duration is lacking. Here, we report primary results from LEROS, a Phase 4, externally controlled interventional study in patients with subacute/dynamic LHON treated with idebenone for up to 24 months.

Methods: Patients with LHON onset ≤5 years prior were enrolled and stratified by time since onset: subacute/dynamic (≤1 year) and chronic (>1 year). Visual acuity (VA) outcomes from 181 patients, treated for up to 24 months were compared to retrospective data from an external natural history (NH) cohort (N = 372) matched by time since onset. Outcome measures, from baseline, were clinically relevant recovery (CRR): improvement from ‘off‐chart’ VA to at least 1.6 logMAR, or a ≥0.2 logMAR improvement if already ‘on‐chart’; clinically relevant stabilization (CRS): maintenance of VA < 1.0 logMAR; and clinically relevant benefit (CRB): reaching a CRR, a CRS, or both.

Results: The primary endpoint – the proportion of subacute/dynamic eyes with a CRB from baseline following 12 months of treatment, versus matched NH eyes – was met (42.3% [60/142] vs. 20.7% [40/193] [p = 0.0020]); this difference was maintained after 24 months (52.9% [64/121] vs. 36.0% [27/75] [p = 0.0297]). The difference in the CRB rate was largely driven by CRS, occurring in 64.5% (20/31) of eligible (<1.0 logMAR at baseline) treated eyes versus 22.5% (9/40) of eyes in the NH cohort at 12 months (p = 0.0005). The proportion of off‐chart patients (best VA) continuously decreased after the likely nadir at 6 months. By 24 months, a larger proportion of patients had moved into the non‐legally blind category than at BL (42.9% vs. 33.9%).

Conclusions: LEROS corroborates previous idebenone efficacy results, demonstrating that long‐term treatment is well tolerated and results in prolonged clinical benefit in patients with LHON in the subacute/dynamic phase.
Characterization of tear dynamics
Authors: Ramasubramanian Darshan , Alonso José Manuel López , Verdejo Jose Luis Hernandez , Costa David Madrid
Published: December 2022

Purpose: Tear film is important in eye optics due to its influence on dry eye, contact lenses fit, etc. After blinking, it starts to evaporate causing the film to thin. While thinning in the eye center, the tear maintains a constant thickness around the eyelids (meniscus), which is easy to measure. This work aims to study tear film dynamics based on the meniscus and dry eye‐related parameters.

Methods: A hybrid OCT‐iVue was used to measure the lower meniscus for several subjects. The dynamics of the tear were simulated with a precorneal tear film model after blinking [1], introducing the tear geometric parameters as well as physical parameters (viscosity, evaporation, surface tension, etc). The model uses the standard parameters given in [1], changing the values of the meniscus, viscosity, and surface tension to test different patients and dry eye conditions.

Results: The tear film thickness was calculated for patients with the different meniscus. The model shows a tear thinning over time (additional drop before each meniscus). In the central eye, there are slight oscillations that are more pronounced for higher meniscus, increasing pressure. The greater meniscus seems to have greater spatial stability. The method allows the study of the spatial–temporal oscillations of tears and relates them to their physical parameters.

Conclusions: Tear stability appears to be related to the ocular meniscus and greater stability is observed for the larger meniscus. Dry eye characteristics appear with high viscosity and medium surface tension. Additional mathematical studies should be done to clarify the influence of different tear parameters and their measure in different patients.

Reference

1. Braun R.J., et al. Modelling drainage of the precorneal tear film after a blink. Math Med Biol 2003; 20: 1–28.
Retinal vascular abnormalities in children with neurofibromatosis type 1
Authors: Touzé Romain , Abitbol Marc , Bremond‐Gignac Dominique , Robert Matthieu
Published: December 2022

Purpose: Retinal vascular abnormalities (RVA) have been recently described in patients with neurofibromatosis type 1 (NF1) as vascular tortuosity, best visible on infrared imaging. This study assessed clinical RVA's characteristics in a large series of children with NF1.

Methods: This retrospective observational study was conducted in children (0–18 years old) with an NF1 diagnosis. Using near infrared imaging, RVAs were classified according to the nature of vessels involvement and their degree of tortuosity.

Results: Retinal imaging from 140 children, with a median age of 8.8 [1.5–18] years, were included; 52 (37.1%) patients (81 eyes) exhibited RVAs. These RVAs comprised 96% (50/52) of simple vascular tortuosity and 17% (9/52) of cork‐screw pattern. Cork‐screw pattern involved only small veins, while simple vascular tortuosity could affect both arteries and veins. No statistically significant age correlation was observed, but evolution of RVAs from simple vascular tortuosity to cork‐screw pattern was observed in 5 cases.

Conclusions: Retinal vascular abnormalities occurred in 37.1% of children with NF1. These abnormalities may result from NF1 promoting localized tortuosity in both small arteries and veins, while only small second or tertiary order venules evolve to highly tortuous pattern.
Difference of corneal endothelial characteristics of diabetic and non‐diabetic cataract patients who underwent phacoemulsification at Dr Saiful Anwar hospital Malang
Authors: Yamin Nidia Astriani , Handayani Nina , Sujuti Hidayat
Published: December 2022

Purpose: To compare the corneal endothelial characteristics of diabetic and nondiabetic cataract patients who underwent phacoemulsification.

Methods: A retrospective study, data collected from medical records of patients who visited Cataract and Refractive Surgery Outpatient Clinic and underwent phacoemulsification at Saiful Anwar Hospital Malang, the tertiary hospital in East Java, Indonesia, between April 2021 to January 2022. Data collected regarding corneal endothelial condition were endothelial cell density (ECD), hexagonality and Coefficient variation (CV) examined using Specular Microscope (Nidek, CEM 530).

Results: There were 32 eyes from 31 patients, consist of 55% men and 45% women, 17 eyes diabetic and 15 eyes non‐diabetic. The most common age range is 40–49 years old (35.5%). Baseline ECD and hexagonality were higher in diabetic compared to non‐diabetic patients (2781.35 ± 283 vs 2625.88 ± 389 and 67.71 ± 4 vs. 65.81 ± 4, respectively), while baseline CV was lower in diabetic patients (30.4 ± 4 vs. 33.2 ± 6) (p > 0.005). There was a decrease of ECD and hexagonality, but increase of CV after surgery in both groups (p > 0.005).

Conclusions: There was significant decreased of ECD and Hexagonality but increased CV in diabetic group on pre phacoemulsification compared to post phacoemulsification. There are no statistically significant difference of baseline and endothelial damage between diabetic and non‐diabetic.
Brain‐derived neurotrophic factor‐mimetic compounds in biodegradable microspheres as novel neuroprotective approaches for retinal diseases
Authors: Brugnera Marco , Messina Flavia , Reynolds Alison , O'Reilly Niall , Kalesnykas Giedrius , Herrero‐Vanrell Rocío , Kennedy Breandán , Bravo‐Osuna Irene
Published: December 2022

Purpose: Neuroprotectants can modulate cell survival and molecular pathways common to several inherited retinal degenerations (IRD). Among them, 7,8‐dihydroxyflavone (7,8‐DHF), a brain‐derived neurotrophic factor (BDNF) mimetic, proved to rescue vision in dyeucd6 zebrafish model of IRD by upregulating BDNF–TrkB signalling [1]. A novel 7,8‐DHF structural analogue, namely OPGG‐A2, demonstrated an improved ability in restoring visual capacity. Considering these results, this work aims at evaluating long‐release devices loaded with the two neuroprotectants as possible therapies for chronic retinal diseases.

Methods: Biodegradable poly(lactic‐co‐glycolic)acid(PLGA) microspheres (MS) were prepared following the oil‐in‐water emulsion solvent evaporation technique. 7,8‐DHF and OPGG‐A2 were separately included in ratio 1:10 with PLGA(w/w). MS loaded with 7,8‐DHF (FMS) and with OPGG‐A2 (A2MS) were characterized in terms of production yield, internal and external morphology, particle size, encapsulation efficiency and in vitro release profile.

Results: After sieving and freeze‐drying processes, 38–20 μm (38MS) and 20–10 μm (20MS) particle sizes were selected as suitable to fit conventional 30‐gauge needles for intravitreal administration. Both the granulometric fractions followed a unimodal distribution for both FMS and A2MS. Both FMS and A2MS demonstrated spherical shape without presence of crystal inside and on the 38MS and 20MS surfaces. FMS showed high encapsulation efficiencies (53.4 ± 3.4 μg/mg 38MS; 30.7 ± 12.2 μg/mg 20MS) as A2MS (58.8 ± 5.6 μg/mg 38MS; 61.3 ± 1.0 μg/mg 20MS). Both drugs were released in a sustained manner during 30 days after a high burst release under the experimental conditions specified (13.7 ± 1.4 μg/mg FMS‐38MS; 11.4 ± 3.8 μg/mg FMS‐20MS; 11.5 ± 2.2 μg/mg A2MS‐38MS; 23.1 ± 1.7 μg/mg A2MS‐20MS).

Conclusions: The two formulations managed in vitro liberating both 7,8‐DHF and OPGG‐A2 for 1 month and could be interesting as prototypes for testing long‐term intravitreal neuroprotective therapies.

References

1. Daly C, Shine L, Heffernan T, et al. A brain‐derived neurotrophic factor mimetic is sufficient to restore cone photoreceptor visual function in an inherited blindness model. Sci Rep 7, 11 320 (2017).