bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of COVID‐19 on intravitreal injections of anti‐vascular endothelial growth factor (VEGF): experience of a tertiary center in Tunisia
Authors: Aoun Safa Ben , Maamouri Rym , Ouederni Meriem , Nefaa Fehmy , Nabi Wijden , Cheour Monia 
Published: January 2022

AbstractPurposeTo report the clinical experience of intravitreal injections of anti‐VEGF at a tertiary center of ophthalmology department in Tunisia during the COVID‐19 pandemic.MethodsRetrospective comparative cross‐sectional study describing the clinical experience of the ophthalmology department in Habib Thameur Hospital in Tunis, Tunisia from the 1st of March 2019 to the 1st of March 2021. Diagnosis, intravitreal injection history, medical history, ophthalmic examinations data were collected and analyzed.ResultsFrom the1st of March 2019 to the 1st of March 2021, 2463 intravitreal injections of anti‐VEGF were made. The main etiologies were diabetic macular edema in 2003 eyes (82%), age‐related macular degeneration in 284 eyes (12%), retinal vein occlusion in 127 eyes (5%), and other macular diseases in 49 Eyes (1%). Before the Covid‐19 pandemic, from Mars 2019 till February 2020, we made 78 injections per month with only three cases of neovascular glaucoma (NVG) and two cases of vitreous hemorrhage. During the two months of national Covid lockdown, the total number of injections decreased to 39 injections per month. After the lockdown, the number of injections monthly had increased to 138 injections per month. There were no changes in the prevalence of responsible diseases (p = 0.29). Therefore, despite the increase of the number of injections, from May 2020 till March 2021, the number of NVG had risen to 16 and the vitreous hemorrhage to 27 (p = 0.03).ConclusionsCOVID‐19 pandemic has dramatically affected the management and the treatment of eye diseases, and has resulted in a significantly worse short‐term outcomes and more severe ocular impairment.
Establishing intranasal administration as an alternative to intravitreal delivery of fluorescent annexin
Authors: Hill Daniel , Luong Vy , Guo Li , Cordeiro M. Francesca 
Published: January 2022

AbstractPurposeDARC (detection of apoptosing retinal cells) facilitates in vivo assessment of retinal pathology using a confocal laser scanning ophthalmoscope. The technology uses fluorescent annexin to mark unhealthy cells in the retina. In vivo imaging of intravitreally administered DARC allows for a unique assessment of neuronal health, applicable to a broad range of neurodegenerative pathologies. To avoid both the potential complications and discomfort arising from intravitreal administration, intranasal delivery of DARC was investigated as an alternative route of delivery.Methods5 female 3xTg transgenic Alzheimer’s disease (3xTg‐AD) model mice were used as a model of retinal cell death and 5 C57 mice were used as healthy controls (all animals from The Jackson Laboratory). Intranasal DARC administration involved restraining the animal and applying 5 µL of DARC to each nostril. Retinas were imaged in vivo at baseline and 2 hours after DARC administration a Multiline Spectralis OCT. Animals were then sacrificed, and the retinas were extracted, fixed, and imaged with fluorescent microscopy. Spots were counted using an automated image analysis script for in vivo images.ResultsIntranasal DARC demonstrated discrimination between healthy and diseased eyes in vivo (significantly more spots in disease; p < 0.05) and produced images of similar quality to those acquired from animals receiving intravitreal DARC. A higher intranasal DARC dose was required compared to intravitreal administration (approximately 10‐fold increase).ConclusionsIntranasal DARC has been shown as a viable alternative to intravitreal administration, thus helping to refine animal procedures. Optimisation of an intranasal buffer to enhance delivery and reduce dose, followed by expansion to rat models are to be established in future work. In the long term, standardisation of administration route to intranasal across animal and human applications may help to improve the applicability of DARC‐based research.
Corneal biomechanics in a pediatric population
Authors: Corbu Cătălina Gabriela , Potop Vasile , Coviltir Valeria , Constantin Mihaela Monica , Dăscălescu Dana‐Margareta Cornelia , Burcel Miruna Gabriela , Ionescu Cătălina Ioana , Corbu Maria‐Cristina 
Published: January 2022

AbstractPurposeThe purpose of the study is to explore the relationship between biomechanical corneal parameters and axial length in a pediatric population.MethodsWe conducted a prospective study that included 82 eyes from 41 pediatric patients. All patients were submitted to a complete ophthalmologic examination that included autorefractometry (before and after pharmacological cycloplegia), slit lamp and fundus examination, ocular tonometry. Additionally, the patients underwent examination with Ocular Response Analyzer (Reichert Ophthalmic Instruments Inc., Depew, NY) to determine corneal hysteresis (CH), corneal resistance factor (CRF) and with Aladdin biometer (Topcon, Tokyo, Japan) to determine axial length (AL) and central corneal thickness (CCT). Statistical analysis was performed using IBMSPSS Statistics 26.ResultsOur study included 82 eyes, from 41 patients (63.41% female, 36.59% male). The average age was 13.29 years old (12.92 in females, 13.93 in males). Average CH, CRF, and spherical power, respectively, were similar between sexes: 12.30 mmHg, 12.47 mmHg, −0.70 D respectively in females, 12.89 mmHg, 13.31 mmHg and −1.27 D respectively in males. Mean AL and CCT are larger in males than in females, in a statistically significantmanner. Average AL is 23.69 mm in females, 24.52 mm in males (p = 0.007) and average CCT is 0.558 mm in females and 0.583 mm in males (p = 0.003). We also found a statistically significant moderate negative correlation between CH and AL in the pediatric population (Pearson’s r of −0.350, p = 0.001), and also in both sexes (Pearson’s r of −0.419, p = 0.002 in females and −0.437, p = 0.016 in males).ConclusionsOur study reveals that in the pediatric population, at similar age, males have a thicker central cornea and longer axial length. Furthermore, in these patients, a high axial length is correlated to a low corneal hysteresis. Further studies are needed to explore these data and to confirm these findings in adults.
Full‐thickness central corneal grafts in tectonic lamellar sclerokeratoplasty for malformative, invasive and inflammatory limbal insufficiency treatment
Authors: Amatu Jean‐Baptiste , Wei Leo Seo , Nathalia Bellon , Christine Bodemer , Bremond‐Gignac Dominique 
Published: January 2022

AbstractPurposeTo describe the surgical technique and to assess the outcomes in pediatric patients who underwent tectonic lamellar sclerokeratoplasty using full‐thickness central corneal grafts to treat malformative, invasive and inflammatory limbal insufficiency.MethodsRetrospective, multicenter, non‐comparative analysis of a consecutive interventional case series including five pediatric cases of progressive limbal insufficiency from various severe malformative and inflammatory cause. All patients underwent tectonic lamellar sclerokeratoplasty using full‐thickness central corneal grafts under general anesthesia. Progression of limbal insufficiency after surgery, preoperative and postoperative visual acuity and perioperative complications were recorded retrospectively from patient medical records and external eye imaging.Minimum post‐operative follow‐up was 6 months for each patient.ResultsIn total, 5 children with severe limbal insufficiency from various etiologies were included. Mean age at surgery was 5.6 yo (range 5 w to 11 yo). Four (80%) had severe progressive and invasive choristomas and one (20%) presented a severe case of epidermolysis bullosa.Two cases (40%) showed a stabilization of the postoperative visual acuity, other cases had non‐quantifiable visual acuity due to various reasons. Four cases (80%) presented a stabilization of the limbal insufficiency and corneal opacification. Two cases (40%) of corneal graft opacification without consequences on visual acuity were noted. One case (20%) of corneal graft infection was followed by limbal insufficiency recurrence. A second procedure for recurrence was performed in one case (20%).ConclusionsUsing full‐thickness central corneal grafts in lamellar sclerokeratoplasty for severe malformative, invasive and inflammatory limbal insufficiency cases seems to help reducing progression. In most of the cases, stable visual acuity was maintained or visual axis preserved, with limited postoperative complications.
Evaluation of retinal nerve fiber and ganglion cell layers in patients with multiple sclerosis and fibromyalgia
Authors: Palomar Elisa Viladés , Ciordia Beatriz Cordón , Rodrigo Maria Jesus , Perié Manuel Subías , Campo Lorena Arias , Altabás María José Vicente , Tello Alvaro , Castro‐Roger Luisa , Garcia‐Martin Elena 
Published: January 2022

AbstractPurposeTo assess the differences in the retinal nerve fiber layer (RNFL) and ganglion cells (GCL) between patients with multiple sclerosis versus fibromyalgia. Likewise, to evaluate the ability of the Posterior Pole protocol from Spectralis Optical Coherence Tomography (OCT) to detect clusters with differences between these groups.MethodsWe analyzed 100 eyes of healthy subjects (CS), 100 eyes of patients with relapsing‐remitting multiple sclerosis (RR‐MS) and 55 eyes of patients with fibromyalgia (FB). The thickness of the RNFL and the GCL between these groups were evaluated in the 64 cells of the macular grid analyzed by the Posterior Pole protocol and later the thickness maps and cluster detection were reproduced thanks to the matrix analysis using Matlab (Mathworks,USA). Additionally, the RR‐MS group was compared with the different fibromyalgia phenotypes (atypical, biological and depressive).ResultsBoth pathologies present a very similar significant thinning (p < 0.05) of both layers compared to healthy subjects. Compared with healthy controls, significant differences were found for the RNFL in the papillomacular bundle area and for the GCL in the macular area in RR‐MS group and fibromyalgia patients. Additionally, no significant differences were observed between patients with RR‐MS and those with fibromyalgia.ConclusionsFor the last years, the GCL has been postulated as a potential biomarker of neurodegenerative processes. Both RR‐MS and fibromyalgia present a similar thinning of the RNFL and GCL, although it is greater in patients with RR‐MS. Observed alterations are more significant in the GCL, thus suggesting that fibromyalgia might be a neurodegenerative process, with results similar to those observed in other well studied degenerative processes.
Early and late effects of botulinum toxin in infantile esotropia
Authors: Ciftci Suleyman 
Published: January 2022

AbstractPurposeTo observe the short‐ and long‐term effects of botulinum toxin in infantile esotropia.MethodsBetween February 26th of 2013 and January 27th of 2015, botulinum toxin was injected transconjunctival to bimedial rectus of 5 patients. Following, one patient was checked regularly until their 8th year, one 9th month, one 7th month, one 3rd month, one 1st month. During their regular follow‐up parents were instructed to patch the dominant eye either in consecutive exotropia or esotropia phases. And also, they were assisted on glass prescription. Further, patients were seen again between their 78th and 96th months to find out their current visual acuity and to observe if they had any late term accompanying squints.ResultsBased on our observation derived from the follow‐ups: After the 3rd month on the horizontal plan, orthophoria on 2 patients, monocular esotropia on 2 patients and orthophoria with dissociated horizontal deviation (DHD) developed on 1 patient. On exotropia stage, for 3 hours a day patching was applied on the dominant eye. Inferior oblique muscle hyperfuction (IOHF) developed on all the patients at the earliest 2nd month and at the latest 7.5th year. Dissociated vertical deviation (DVD) and latentnystagmus did not develop on any patient, DHD developed on 1 patient. On the last examination, patients’ visual acuities were determined. On the orthophoric ones who had IOHF development: on his 7.5th year had 1.0/1.0 visual acuity, on her 9th month had 0.4/0.6 visual acuity, and on her 2nd month had 0.2/0.2 visual acuity. In this state, there seems to be an inverse proportion between visual acuity and IOHF development. Monocular esotropia ones: on the strabismic eye 0.1, on the dominant eye full vision was described. These patients were not compliant on their follow‐ups so when IOHF development happened was not determined.ConclusionIt seems botulinum toxin injection gives a chance for restoration of visual immaturity, and by this way infantile esotropia can be made to behave almost similarly to acquired esotropia.
Ophthalmologic Microvascular changes in Wolfram syndrome
Authors: Maria Cunha Ana , Barbosa‐Breda João , Grangeia Ana , Estrela‐Silva Sérgio , Carneiro Ângela , Falcão‐Reis Fernando , Faria Olinda 
Published: January 2022

AbstractPurposeTo evaluate ophthalmic, systemic, genotype features and microvascular abnormalities of patients with Wolfram syndrome (WFS).MethodsCross‐sectional, prospective evaluation of consecutive patients with WFS and healthy subjects. WFS diagnosis was performed based on the clinical presentation and detection of biallelic pathogenic variants in the WFS1 gene. All patients underwent a complete ophthalmological examination and a retinal vasculature evaluation by OCT‐A. Quantitative analysis included: whole‐image vessel density (VD, %), inside disk VD and peripapillary VD of the ONH and peripapillary region, as well as, whole VD for parafoveal superficial capillary plexus (SCP) of the macula.ResultsFifty‐eight eyes were included in this study, 26 eyes from patients with WFS and 32 eyes from healthy subjects. Seven families were included, twelve patients had biallelic pathogenic variants whereas one had one pathogenic variant in the WFS1 gene confirming the diagnosis of WFS type 1 and Wolfram‐like syndrome, respectively. Optic atrophy and diabetes mellitus were the most common systemic findings. The best corrected visual acuity (BCVA) ranged from light perception to 0.1 logMar. Quantitative evaluation demonstrated a significant difference between WFS and healthy subjects on whole‐image VD, inside disk VD, and peripapillary VD (p < 0.001 for all) and SCP perfusion density (p < 0.001). Ganglion cell complex (GCC) and retinal nerve fiber layer (RNFL) thickness have significant decrease in WFS patients with BCVA more than 1 logMar compared to those with less than 1 logMar (p < 0.001 and p = 0.024, respectively).ConclusionsWFS patients had a decreased of vessel density in ONH, peripapillary microvasculature and in macular microvascular networks. Microvasculature changes seem to occur before a severe decrease in visual acuity, and the decreased of the GCC and RNFL thickness.
Ocular biodistribution of once‐daily bilastine eye drops reveals highest levels in conjunctiva up to 24 hours post‐administration
Authors: Torrens Prat Inés , Gonzalo Ana , Ganza Álvaro , Hernández Gonzalo , Zazpe Arturo 
Published: January 2022

AbstractPurposeA novel effective, safe and well tolerated topical formulation of bilastine, a second‐generation H1‐antihistamine, has been developed for allergic conjunctivitis treatment. This in vivo biodistribution study aimed to determine the exposure to topical bilastine of different ocular tissues and verify if the evolution of conjunctival levels over time supports the intended once daily posology.MethodsTwenty‐four Dutch‐Belted rabbits received 30 µl/eye of 6 mg/ml bilastine formulation (a preservative free artificial tear containing sodium hyaluronate). Blood samples were obtained through the ear artery. Three animals were sacrificed per time point, and aqueous and vitreous humor, cornea, conjunctiva, iris/ciliary body, crystalline lens and retina/choroid samples were collected from both eyes. Bilastine concentrations in matrices were determined by validated LC‐MS/MS methods and pharmacokinetic parameters were determined usin a non‐compartmental analysis.ResultsBilastine Cmax was achieved from 30 min to 6 h after drug administration. Bilastine exposure was highest in conjunctiva (Cmax: 2545.04 ng/g, at 6 h post‐administration; AUCt: 11382.40 ng·h/g) and cornea (Cmax: 609.11 ng/g, at 1 h post‐administration; AUCt: 1993.88 ng·h/g), followed by the iris/ciliary body, retina/choroid, aqueous humor, plasma, vitreous humor, and crystalline lens. Quantifiable bilastine concentrations were observed up to 24 h post‐instillation in conjunctiva (388.45 ng/g), cornea (28.68 ng/g), iris/ciliary body (12.42 ng/g), retina/choroid (1.91 ng/g) and crystalline lens (0.12 ng/g). In plasma, aqueous and vitreous humor, bilastine was detected up to 12 h post‐administration.ConclusionsThe results show the preferential distribution of bilastine eye drops in the conjunctiva, the intended target tissue, while absorption is limited and potential for systemic side effects low. Significant levels of bilastine found in conjunctiva up to 24 h post‐dose support the once daily posology.
A smart phone app for individual risk assessment for progression of diabetic retinopathy
Authors: Scholtz Sibylle , Aspelund Thor , Einarsson Stefan , Gudmundsdottir Arna , Jonsdottir Sigurbjörg , Thor Steinasson Aegir , Stefansson Einar 
Published: January 2022

AbstractPurposeCreation of a smart phone application containing diabetic retinopathy risk calculator to empower individual diabetic patients to understand their personal risk factors and risk profile. Educate and motivate patients to influence these risk factors.MethodsA previously validated and published diabetic retinopathy risk algorithm (Aspelund et al 2011; Lund et al 2016) was programmed as a smart phone application. Clinical data can be entered by hand or through the digi.me platform, which is available in an increasing number of countries for automatic transmission of clinical data.ResultsThe app is available at no cost in app stores and can be found under search word “retinarisk”. User numbers and responses will be reported.ConclusionsA smartphone app is now available at no cost for all diabetic patients. The app allows each patient to evaluate his/her personal risk for progression to sight threatening diabetic retinopathy. The app provides education about diabetic retinopathy and risk factors and motivates and informs the patient to modify and improve the risk profile. The app is a step in the direction to empower individual patients through validated interpretation of available clinical data: what these data mean for each individual, how the risk factors can be modified for risk reduction. It provides a personal prognosis for retinopathy progression.
Hyperspectral retinal imaging in mouse models of proteinopathies identifies disease‐specific signatures
Authors: De Groef Lies , Veys Lien , Hadoux Xavier , Vandenabeele Marjan , Lemmens Sophie , Serneels Lutgarde , Theunis Jan , De Strooper Bart , Stalmans Ingeborg , van Wijngaarden Peter , Moons Lieve 
Published: January 2022

AbstractPurposePrevious research in the AppNL‐G‐F mouse has shown that hyperspectral retinal imaging (HSRI) can be used to quantify retinal amyloid burden in the preclinical stages of Alzheimer’s disease (AD) [1]. This underscores its potential as an imaging biomarker for AD diagnosis and monitoring. One prerequisite for the rational implementation of HSRI as a biomarker, however, is a better understanding of the pathological correlate of the HSRI signature. In this follow‐up study, we explored HSRI signatures in different proteinopathies and identified the pathological features underlying the observed HSRI results.MethodsRetinal tissues were collected from mouse models with amyloid, tau and alpha‐synuclein overexpression/aggregation for ex vivo HSRI (Snapscan, Imec) [1]. HSRI was complemented with optical coherence tomography and electroretinograms (prior to HSRI) and immunohistochemistry and molecular studies of protein aggregation (after HSRI).ResultsWhile all protein aggregates led to HSRI changes in the 450–600 nm range, distinct signatures were observed for amyloid, tau and alpha‐synuclein. Furthermore, the observed HSRI changes correlated with levels of the protein oligomerization and aggregation. Diverging patterns of retinal dysfunction/degeneration were observed in the different mouse models, illustrating the varied impacts of these protein aggregates on retinal structure and function.ConclusionsHSRI may be used to quantify retinal amyloid, tau and alpha‐synuclein, underscoring its potential as a biomarker for diagnosis and disease monitoring. Moreover, our data suggest that amyloid, tau and alpha‐synuclein accumulation lead to distinct HSRI signatures, thus adding further evidence that HSRI may have utility in the diagnosis and stratification of proteinopathies associated with the most common forms of neurodegenerative diseases.BibliographVandenabeele et al. (2021) Acta Neuropathol Commun 9(1):6.
QR‐421a RNA therapy in retinitis pigmentosa due to mutations in USH2A: Stellar trial Phase[AP1] 1b/2 interim results
Authors: Audo Isabelle , Birch David G. , Thiran Jayasundera K. , Meunier Isabelle , Huckfeldt Rachel M. , Koenekoop Robert K. , Yang Paul , de Cock Edouard P. M. , Dahler Ellen C. , Taylor John , Shams Naveed , Girach Aniz 
Published: January 2022

AbstractPurposeTo report Phase 1b/2 interim results of QR‐421a RNA therapy promoting USH2A exon 13 skipping. USH2A exon 13 mutations lead to non‐syndromic Retinitis Pigmentosa & Usher syndrome type 2.MethodsStellar (NCT03780257) is a 24‐month, multicenter Phase 1b/2 single‐dose trial assessing 3 dose levels (50, 100, 200 μg) of QR‐421a in patients aged ≥18 years with biallelic USH2A pathogenic mutations with at least one in exon 13. Cohorts 1 & 2 included subjects randomized to sham‐procedure or QR‐421a. Primary endpoints: frequency & severity of adverse events (AEs). Secondary endpoints: change in best‐corrected visual acuity (BCVA), static perimetry & ellipsoid zone [EZ] area.Results20 subjects were enrolled, 14 received QR‐421a & 6 received sham. Response to QR‐421a was similar for all doses. No serious AE or inflammation was observed. Two subjects had worsening of pre‐existing conditions: one with cataracts (not treatment‐related) & one with cystoid macular edema (being managed with standard care). BCVA stabilization was observed in QR‐421a‐treated eyes (TE), versus a decline in untreated eyes (UE). At week 48, mean BCVA benefit was 6.0 & 9.3 letters in all QR‐421a‐treated & advanced subjects (n = 6; baseline BCVA of <70 letters) respectively. No BCVA benefit was observed in sham‐treated eyes (SE). Mean change from baseline of the EZ‐area was +15.0% in TE, –26.4% in UE, & –12.5% in SE at week 24. For static perimetry at week 12, the mean number of locations (loci) that improved by ≥7 dB compared to baseline was 9.2 loci versus 6.1 loci in TE versus UE in all QR‐421a‐treated subjects & 12.9 loci versus 6.9 loci in early moderate‐stage subjects (n = 8; baseline BCVA of ≥70 letters). SE responded similarly to UE.ConclusionsQR‐421a was well tolerated & demonstrated evidence of disease stabilization in visual acuity, & improvements in retinal sensitivity & retinal structural imaging data. An open‐label extension trial & 2 Phase 2/3 trials are planned.