bluuebunny/crossref_metadata_2025 huggingface dataset:
Light‐field fundus imaging under astigmatism – An eye model study
Authors: Schramm Stefan , Dietzel Alexander , Blum Maren‐Christina , Link Dietmar , Klee Sascha
Published: January 2022

Purpose

One strong risk factor for glaucoma is a suspicious optic nerve head appearance and an increase in depth. With the upcoming light‐field (LF) technology one‐shot 3D retinal imaging and measuring is possible. Due to optical aberrations such as astigmatism, the imaged depth can be distorted. The study presented here investigated the influence of astigmatism on LF image quality and depth estimation using an eye model.

Methods

We developed a new eye model that added astigmatism by integrating an additional cylindrical lens between the cornea and lens. We used cylindrical lenses from −4 to 0 dpt in 1 dpt steps in vertical and horizontal orientations. The fundus was modelled as a half hollow sphere with a radius of 10 mm and a central papilla with 0.8 mm depth. The fundus was coated with red acrylic lacquer, and vessels were drawn with a thin brush with black acrylic lacquer. LF fundus images (15 for each cylindrical lens and orientation) were taken with a fundus camera (FF450, Carl Zeiss Meditec AG, Germany) equipped with an industrial LF camera (RX12, Raytrix GmbH, Germany). Depth measurements were performed with the Raytrix LF software (RxLive 5.0.046.0) as difference from a vertical vessel to a horizontal orientated vessel. The same measuring point was used for all images.

Results

The LF images taken with a cylindrical lens show a visually poorer image quality. Depth estimates were only possible in the central image area. The fundus images show increasing depth differences between vertical and horizontal vessels with increasing astigmatism up to 0.37 mm at −4 dpt in contrast to the flat imaged fundus without cylindrical lens. The sign of the depth differences changes when the orientation of the inserted cylindrical lens is changed.

Conclusions

The imaged LF of a fundus of an astigmatic eye model is measurably distorted and affects vertical and horizontal structures differently. This must be taken into account when evaluating and interpreting LF depth measurements.
VSN16S, an agonist of the cannabinoid receptor, reduces IOP profiles and exhibits neuroprotective properties in a rat model of glaucoma
Authors: Guo Li , Luong Vy , Gregson Aaron , Baker David , Selwood David , Cordeiro M. Francesca
Published: January 2022

Purpose

There is an unmet need for new drugs in glaucoma that can effectively prevent glaucoma progression. We assessed the effects of VSN16S and AG‐020, the agonists of the cannabinoid receptor, on intraocular pressure (IOP) and neuroprotection using a rat model of ocular hypertension (OHT).

Methods

20 male Dark Agouti (DA) rats aged 8–10 weeks were randomly located into 4 groups (n = 5): OHT‐only, OHT+vehicle, OHT+VSN16S, and OHT+AG‐020. All animals had IOP surgically elevated in the left eye (OS) by injection of hypertonic saline into the episcleral veins. Except for OHT‐only, animals in the other 3 groups have received eye drops in OS either vehicle or VSN16S or AG‐0202 at 10 mg/ml, twice daily for 3 weeks following OHT‐induction. IOPs were recorded in both eyes at baseline (BL), day1, week1, 2, and 3 using a Tonopen. Animals were in vivo imaged for retinal ganglion cell (RGC) apoptosis in both eyes using DARC (Detection of Apoptotic Retinal Cells) at BL and week3 before culled. Retinal whole‐mounts were immunostained with a Brn‐3a antibody to assess RGC survival. DARC spots and RGC counts were assessed by blinded algorithm analysis.

Results

Surgical procedure induced a significant increase in IOP profiles in all animal groups compared to the contralateral eye (OD), and peak levels occurred at day1 (p < 0.001). In the OHT eyes treated with VSN16S, IOPs at week1 exhibited a sharp reduction (p < 0.05), and integrate IOP at week3 was significantly lower than vehicle controls (p < 0.01). However, AG020 showed no effect on IOP. IOP elevation resulted in a significant increase in DARC counts (RGC apoptosis) in all groups, compared to the baseline. DARC counts revealed a significant reduction in the OHT eyes treated by VSN16S, compared to the OHT‐only and vehicle groups (p < 0.01), but less of a reduction of DARC counts was observed with AG‐020 treatment (p < 0.05). A significant reduction of Brn‐3a+RGC density was seen in the OHT‐only group compared to naïve controls (p < 0.05), and VSN16S treatment demolished the difference although no significance was found on Brn‐3a+RGC density between VSN16S and controls.

Conclusions

VSN16S exerted neuroprotective properties in OHT‐induced RGC loss, which may be associated with lowering IOP profiles. DARC is a useful tool in the assessment of drug efficacy in retinal neurodegenerative diseases.
The iVAN Project: an innovative solution to meet the challenges in trial recruitment during a global pandemic
Authors: Abdulhussein Dalia , Margai Gina , Manzar Haider , Yap Timothy , Bonetti Jessica , Bonetti Paolo , Miodragovic Serge , Normando Eduardo , Cordeiro Francesca
Published: January 2022

Purpose

COVID‐19 has greatly affected the number of patients willing and able to attend hospital, with research activity also greatly impacted. Imperial College Ophthalmology Research Group (ICORG) have observed clinical backlogs and a 77% decrease in trial patient recruitment. As a first of its kind, this project aims to combat clinic waiting lists and patient confidence in trial involvement through creating a safe, flexible and decentralised healthcare environment with iVAN, a mobile research unit.

Methods

A survey of outpatients was performed exploring attitudes towards visiting hospital for clinical and research reasons amidst a pandemic. A vehicle was equipped with state‐of‐the‐art clinical research facilities in a COVID‐safe environment. A multi‐stage approach was taken in order to achieve relevant driving and roadworthiness certification, multi‐disciplinary involvement and healthcare network planning in order to ensure the smooth progression of the project. A pilot period of clinical visits was carried out and evaluated in close vicinity to the hospital.

Results

Of the 53 patients surveyed, 60% percent of patients were not willing to take part in clinical trials with others having concerns related to travel and being in the hospital. The final layout of the vehicle includes imaging devices, a visual field analyser, IT equipment and space for staff to see patients. Social distancing and infection control have been ensured to provide a pleasant and safe working environment. A pilot period is underway assessing staff and patient satisfaction along with capacity and trial data runs, with future plans involving satellite clinics in the community.

Conclusions

Flexible and innovative service provision continues to be required to minimise morbidity attributable to the pandemic. The iVan has the facilities to bring decentralised, specialist ophthalmic care into local communities in a COVID‐safe manner, whilst being a useful tool to engage future research participants.
Vision‐related quality of life in spondyloarthritis patients with history of acute anterior uveitis under treatment with golimumab: preliminary results of the GO‐VISION observational study
Authors: Leal Ines , Jose Patricia , Barão Rafael , Mano Sofia , Melo Ana Teresa , Dourado Eduardo , Tenazinha Catarina , Vaz Cláudia , Ferreira Joana Fonseca , Dinis Sara , Santos Filipe Cunha , Fernandes Henrique , Khmelinskii Nikita , Marques‐Neves Carlos , de Sousa Elsa Vieira , Fonseca João Eurico
Published: January 2022

Purpose

Acute anterior uveitis (AAU) is one of the most common extra‐articular manifestations of spondyloarthritis (SpA), causing significant burden in quality of life (QoL). Golimumab (GLM) is a tumor necrosis factor‐inhibitor proven to be effective and safe in SpA. The GO‐EASY Study provided evidence that GLM decreases the AAU occurrence rate in SpA. Our aim is to study the impact of GLM in the change of vision‐related (VR) QoL in subjects with SpA and past or current AAU.

Methods

Ongoing prospective multicentre observational study (including 8 centres in Portugal) of SpA patients with history of AAU treated with GLM followed‐up for 12 months. We intend to recruit in total 30 patients and we report herein the 6 months outcomes for the first 9 patients enrolled. The occurrence of AAU was assessed in the 2 years before GLM treatment was started and the first 6 months of follow‐up and calculated for the period at risk for a new AAU. VR QoL was assessed with the self‐administered National Eye Institute Visual Functioning Questionnaire‐25 (NEI VFQ‐25). Adverse events were noted.

Results

Nine patients (66.7% female, 100% TNFi‐naive, mean age 46.1 ± 14.4 years (range 22–65)) have completed 6 months of follow‐up. Three patients (33%) were also under oral methotrexate. The mean number of AAU flares in the 2 years preceding the start of GLM was 2.2 ± 1.3 (1–4). During the first 6 months of GLM treatment, the AAU incidence rate was reduced from 1.54 to 0.11 per 100 patient‐years (incidence ratio‐ratio 13.46, 95% CI 2.15–558.00; p < 0.01). At baseline and at 24 weeks after GLM onset, the mean overall index NEI VFQ‐25 total score was 70.2 and 83.2, respectively; improvement in the NEI VFQ‐25 total score was +13 ± 18.2. No significant or new adverse events occurred.

Conclusions

Preliminary data from the GO‐VISION study suggest that GLM is safe and effective in patients with SpA and history of AAU, being able to reduce the AAU occurrence rate and potentially increasing VR QoL.
Phakic implantable collamer lens exchange for high vault with acute angle closure
Authors: Aoun Safa Ben , Ouederni Meriem , Nefaa Fehmy , Nabi Wijdene , Cheour Monia
Published: January 2022

Purpose

To describe a case of an early postoperative angle‐closure related to high vault after phakic implantable collamer lens (ICL) implantation managed by smaller size lens exchange.

Methods

A case report if a 38‐year‐old woman with high myopia underwent refractive surgery correction with posterior phakic Implantable Collamer Lens (ICL) (STAAR Surgical, V4c) in the right eye. White‐to‐white measurement was 12.28 mm. Preoperative anterior chamber depth was 3.04 mm. ICL implantation with a 13.2 mm lens was performed

Results

Postoperative examination showed a shallow anterior chamber with a raised intraocular pressure (IOP) of 28 mmHg. Anterior segment OCT (AS‐OCT) revealed a lens vault of 954 µm raising to 1154 µm after 4 days with iridocorneal angle closure. The diagnosis of acute angle‐closure secondary to non‐pupillary block due to the volume of the ICL was made. Explantation of the ICL and re‐implantation of a smaller sized lens (12.6 mm) was performed 7 days after the first surgery.

Postoperative uncorrected visual acuity was 20/20, IOP was 14 mmHg and no crystalline lens opacities or anisocoria were noticed. The patient achieved a reduction in the vault from 1154 to 596 μm, with an open iridocorneal angle. Specular microscopy showed no significant endothelial cell loss.

Conclusions

Extreme lens vault in our patient was related to poor correlation between pre‐operative measurements and postoperative lens vaulting. AS‐OCT was a helpful tool in diagnosing and managing high vaults with acute angle‐closure. Early ICL extraction in these cases is necessary to avoid angle‐closure glaucoma, severe endothelial loss, and pupillary defect.

Ref‐erence

Arjun Srirampur, Tarannum Mansoori, Pasyanthi Balijepalli, Aruna Kumari Gadde. Management of anisocoria and high vault in an eye with implantable collamer lens. Indian J Ophthalmol. 2020 Dec;68(12):3070–3072.
The landscape of clinical trials research in inherited eye disease
Authors: Ng Vincent , Cornes Paul , Votruba Marcela
Published: January 2022

Purpose

Recent increased understanding of molecular and genetic causes of many inherited eye diseases opens the way to novel therapeutic interventions. The key to drug discovery is in delivering precision targets for treatment that open a therapeutic index over toxicity. We set out to define what type of treatments are emerging, against what targets, and how the trial pipeline is progressing.

Methods

We selected 8 major inherited eye diseases where the primary genetic cause has been established, to identify potential therapeutic target. Data scrutiny and analysis of the clinical trials database on clinicaltrials.gov was performed from 20/3/2021 to 30/4/2021.

Results

We identified 92 trials, of which 33 trials (35.9%) are ongoing or recruiting. Of these 92 trials, 44 trials (47.8%) are completed (but only 14 (31.8%) of these have posted results). 15 trials (16.3%) have an unknown status or are terminated. 52% of the trials are in North America, followed by 29% in Europe and 19% in other parts of the world. Drug intervention accounts for 44% of the trials and 20% are classified as biological intervention. Gene therapy accounts for 13% and 1% are combination intervention trials. Device intervention accounts for 9% with procedure intervention e.g., stem cell transplantation accounting for further 8%. The remaining 5% is classified as others intervention e.g. diet. Some of the trials are in more than 1 phases; 34 of the trials have phase 1 included, 37 trials have phase 2 included and only 10 trials have phase 3 included and this declines to only 1 trial with phase 4 included(a total decrease of 90%). Out of the 15 terminated or status unknown trials, 5 trials are in both phase 1 & 2, 3 trials are only in phase 1, 4 trials are only in phase 2 and 1 trial is only in phase 3. 2 trials are N/A due to device intervention. Combining the data, 8 trials with phase 1 testing included are terminated or with unknown status; 9 trials with phase 2 testing included are terminated or with unknown status. 1 trial with phase 3 testing included is terminated.

Conclusions

Current and future clinical trials in the genetic eye diseases with molecular targets identified have a promising future but the pipeline of translation from phase 1, 2 trials to phase 3 is slow. Nevertheless, the last 5 years has seen a significant increase in therapeutic trials in inherited eye diseases.
Certification of visual impairment in patients with diabetes mellitus in Northern Ireland over a 5‐year period
Authors: Cushley Laura , Peto Tunde , McCann Roseleen , Moutray Tanya , Jonathan Jackson Andrew
Published: January 2022

Purpose

To determine the number of patients with diabetes mellitus (PwDM) who were certified as visually impaired (CVI) over the past 5 years in Northern Ireland, UK.

Methods

CVI data were collected from 11 sites and 50 eye‐specialists using pre‐defined CVI forms. Eye‐specialists must provide patient demographics and vision information such as visual acuity and diagnosis for certification purposes. Data were transcribed into Microsoft Excel before analysis was undertaken to produce an annual CVI report for eye and healthcare professionals. Our analysis determined the contribution of diabetes and diabetic eye disease (DED) to the sight‐impairment burden between 2014 and 2018.

Results

In 2014, 332 CVIs were registered: 184 as severely sight impaired (SSI) and 142 sight impaired (SI). Of the 24 who had diabetes, 19 were certified due to diabetic retinopathy (DR) and 2 to diabetic macular oedema (DMO). Between 2015 and 2017 the number of CVIs increased to 412, 428 and 453 respectively with PwDM having grown to 48, 43 and 41, respectively. PwDM were also certified due to AMD and glaucoma (range of 2%–31% and 2–4% respectively) from 2015 to 2017. After an intense education campaign, in 2018, the total CVI submissions increased to 575; of these 368 were SSI and 196 were SI. The number of people who were certified as having diabetes more than doubled in 2018 to 107 of these, 51 (48%) were certified due to DED. AMD was found to be the second largest cause of visual impairment in PwDM at 40%, the remaining people had other ophthalmic issues such as keratoconus and optic atrophy.

Conclusions

PwDM were previously underrepresented in the sight impaired registers in Northern Ireland. Since the awareness campaign and introduction of improved pre‐defined forms in 2018, Northern Ireland is now on par with certification rates in the rest of the UK. This information provides insight into the epidemiology of sight impairment in Northern Ireland while providing appropriate data for policymaking and service planning purposes.
Assessing the use of telephone consultations to mitigate the effects of social distancing measures for the COVID‐19 pandemic in ophthalmology services
Authors: Kaabneh Ali Khanan , Rigaudy Axelle , Bravo Luciano , Sharma Srilakshmi
Published: January 2022

Purpose

To investigate the change in routine outpatient ophthalmology UK practice during the COVID‐19 pandemic focusing on the use of telephone and video consultation. To determine the views of the UK consultant ophthalmologists on the role of teleophthalmology and its future use.

Methods

A survey was designed to determine teleophthalmology practices pre‐COVID and during the first COVID‐19 lockdown. It also assessed participants’ views concerning the adoption of teleophthalmology and its future application within ophthalmology. The survey recipients were consultants within the UK. The data were collected and analysed using quantitative (SPSS, Chicago, IL, USA) and qualitative (thematic collation) methods.

Results

1. Statistically significant reduction in face‐to‐face workload during the first lockdown.

2. Telephone and video consultation usage increased during lockdown; (93.8 %) of respondents performed telephone consultations and (23.8%) carried out video consultations.

3. (46.25%) of consultants were concerned about the potential negative effect tele‐ophthalmology on training.

4. (52.50%) of consultants did not agree that remote consultation should become the default modality of care (Strongly disagree‐disagree). Although, subspecialties like neuroophthalmology (50%) and oculoplastics (43.48%) supported the adoption of this model.

5. (38.13%) of the consultant body thought that video consultation added value over a telephone consultation.

6. Thematic analysis:

Benefits: efficient in management low risk patients, useful as an adjunct to other services, increase capacity without the space issue and help deal with backlog of patients.

Limitations: Investment into telemedicine hubs is required for it to become more applicable in more fields; not appropriate for some sub‐specialities and risks of missed signs and missed care.

Conclusions

The use of teleophthalmology increased during the first COVID‐19 lockdown. UK ophthalmologists expressed their concern about the negative impact of remote consulting particularly on training. More than 50% disagreed with making tele‐ophthalmology the default modality of care; however, sub‐specialities such neuroophthalmology and oculoplastics perceived that it could be valuable.
Effectiveness of pupillography for assessing the state of autonomic nervous system and the choice of treatment for accommodative disorders in children
Authors: Bushuyeva Nataliia , Dukhayer Shakir , Khramenko Nataliia , Slobodianyk Svitlana
Published: January 2022

Purpose

For the first time, the values of indices of accommodation, direct and friendly pupillary reactions were determined – the maximal (Smax) and minimal (Smin) area of the healthy children aged 6 to 18 years depending on their age and tone of the autonomic nervous system (2016).

Methods

269 healthy children, 130 children with spasm of accommodation and 79 children with accommodation weakness were obsovered. We used the computer pupillography OК‐2 for registration of direct, consensual and accommodative convergent‐pupillary reaction.

Results

Difference between Smax values in children with accommodation spasm (23.94 ± SD 5.5 mm2, DI 95% 22.8–25.0) and with accommodation weakness (49.3 ± SD13.8 mm2, DI 95% 47.1–51.6) was revealed, that can be considered as a criterion for choosing the type of treatment. In accommodation spasm, the pupil area (Smax) in the range 22.8–25.0 mm2 and the general vagotonia (according to the Kerdo index) treatment by mydriatics should be appointed. In weak accommodation, Smax in the range of 47.1–51.6 mm2 and general sympathotonia, transcranial electrical stimulation and phosphenelectrostimulation are indicated. Phosphenelectrostimulation (FES) and ETRANS had unidirectional influence – an increase in the uncorrected visual acuity at a distance of 33% and 49% respectively, an improvement in accommodation reserves of 2.8–4.1 D in patients with accommodative dysfunctions.

Conclusions

The mechanisms of action of electrostimulation, where one of the key roles is the improvement of conduction of nerve fibers. In accommodation spasm and the general vagotonia treatment by mydriatics should be appointed.
Ophthalmological presentation of carotid cavernous fistulas: case series
Authors: Fernandes Carla , Ramos João , Branco Cristina , Costa João
Published: January 2022

Purpose

To describe the clinical presentation of carotid cavernous fistulas (CCFs) managed in Egas Moniz Hospital between January 2010 and September 2020.

Methods

Patients presenting with orbital congestive signs and symptoms with a diagnosis of CCF confirmed by digital subtraction angiography and ophthalmological evaluation were included retrospectively. Clinical presentation and angiographic findings were collected, and a descriptive study was performed.

Results

Ten patients were identified, 7 of which female, with an average age of 62.7 years old. All of our patients presented with ophthalmological complaints. The most frequently seen signs/symptoms were red eye (n = 8), increased intra‐ocular pressure (IOP) (n = 8) and ophthalmoparesis with diplopia (n = 7). Regarding the latter, 5 patients had paresis of the abducens nerve, 1 had a third nerve palsy and another had both. Proptosis and chemosis were observed in 5 and 4 patients, respectively. Tinnitus, fundus abnormalities and decreased visual acuity were reported by 3 patients. One patient presented with headache. In respect to the angiographic classification, 2 were direct and 6 indirect. One case was not classified and the other case refers to an intra‐clival Cognard type IV arteriovenous fistula that drains to the cavernous sinus and therefore closely resembling a CCF. Two patients were managed conservatively, while the remainder were submitted to endovascular procedures. After treatment, the most frequent persistent signs/symptoms were increased IOP (n = 7) and ophthalmoparesis with diplopia (n = 5).

Conclusions

CCFs are rare and difficult to diagnose. Direct CCFs tend to have a more severe, acute onset presentation while indirect CCFs are associated with a more gradual onset and chronic course. In both, anterior and inferior drainages are the most common. Clinical presentation can be varied and nonspecific, however, patients commonly present with ophthalmological manifestations.
Visual outcomes after endoscopic pituitary adenomas surgery: our experience
Authors: Fernandes Carla , Nunes Lídia , Lorga Tiago , Costa João
Published: January 2022

Purpose

To evaluate visual outcomes after endoscopic pituitary adenoma surgery in patients from Egas Moniz hospital between 2013 and August 2020.

Methods

This is a quantitative, observational, retrospective study. Patients with pituitary adenoma with pre‐ and post‐ surgical visual acuity (LogMAR) and chromatic vision assessment, visual field (Octopus®) testing and optical coherence tomography (Heidelberg®) retinal nerve fibers and macular thickness evaluations were included. Visual parameters were subjected to statistical analysis using SPSS T‐test and Wilcoxon test. A statistically significant p‐value was defined as <0.05.

Results

Eighteen patients fulfilled our inclusion criteria. Of the 18 patients, 10 (55.6%) were man, with an average age of 57.4 (±16.5) years old. Fourteen (77.8%) patients had pre‐surgical visual complains for an average of 12.8 (±14.4) months, mostly painless and progressive vision loss 6 (33.3%) and blurred vision 6 (33.3%). Before surgery, most patients (38.9%) already showed contact and opto‐chiasmatic lesion, with an average lesion diameter of 33.1 (±9.2) mm.

The most common histological diagnosis was gonadotrophic adenoma (44.4%) with a low mean aggressiveness (Ki 67) of 2.3 (±1.1). Showed statistical significance the difference between the paired samples (pre‐ vs post‐) “opto‐chiasmatic relationship”, “right eye visual acuity”, “right eye visual field mean sensitivity”, “right eye temporal visual field mean sensitivity”, “left eye visual field mean sensitivity”, “left eye temporal mean sensitivity” and “left eye nasal visual field mean sensitivity”. Concerning improvement in tested variables, 11 (68.8%) patients improved in all variables and 14 (82.4%) improved in at least one.

Conclusions

Our results go with the current scientific evidence that pituitary adenoma resection in patients with preoperative visual symptoms considerably improve these symptoms.
Retinal neurodegeneration and neuroinflammation in a SOD1 mouse model of ALS
Authors: Rojas Lozano María Pilar , Santoyo Manuel Cadena , Fernández‐Albarral Jose Antonio , López‐Cuenca Inés , Salobrar‐García Elena , Hoz Rosa De , Salazar Juan José , Urcelay‐Segura José Luis , Santos‐García Irene , de Lago Eva , Ramírez José Manuel , Ramírez Ana I.
Published: January 2022

Purpose

To determine in a SOD1G93A mouse model (SOD1) of amyotrophic lateral sclerosis (ALS) i) the changes in retinal ganglion cells (RGC) compared to the wild type (WT), and ii) establish whether the microglial activation previously observed in this model corresponds to an M1 or proinflammatory or M2 or anti‐inflammatory microglial phenotype.

Methods

In retinal whole‐mounts of 120‐day‐old animals, from two experimental groups WT (n = 6) and SOD ALS (n = 6), we studied i) the number of RGC with anti‐Brn3a+, and ii) the expression by microglia, labelled with anti‐Iba‐1, of M1 phenotype markers (anti‐IL‐1β and anti‐IFN‐γ) and M2 phenotype markers (anti‐arginase‐I and anti‐IL‐10).

Results

Compared to WT, the retina of SOD1 ALS mice showed: i) a decrease in the number of RGCs, ii) expression by microglia of IFN‐γ and IL‐1β; iii) non‐expression by microglia of IL‐10 and arginase‐I.

Conclusions

These findings demonstrate that in an ALS SOD1model, in an advanced stage of the disease, retinal microglial activation takes place, resulting in a proinflammatory M1 phenotype, which could be related to the loss of RGC. Although ALS is a disease of motor neurons, it can also affect retinal tissue, where a neuroinflammatory and neurodegenerative processes occur.
Child vicious attitude of the head: clinical presentation and etiologies
Authors: Lajmi Houda , El Fekih Lamia , Ben Achour Besma , Hmaied Wassim
Published: January 2022

Purpose

We aim to study the clinical presentation and to detail the etiological investigation of Torticollis.

Methods

Clinical observation of a 7 years old boy, followed in orthopedics for torticollis treated with a neck brace.

Results

Ophthalmological examination showed no elevation of the left eye when adducted, severe limitation of the elevation in straight up gaze, and left eye is depressed instead. The interrogation revealed a history of ocular contusion. We evoked a Brown like syndrome and the patient was treated with a latero‐bulbar injection of Triamcinolone in the orbit supero‐internal angle with a good result.

Conclusions

Torticollis is a dystonic condition defined by an abnormal and asymmetrical head or neck position. It can occur during certain eye conditions to improve the visual acuity (astigmatism, ptosis, early strabismus, nystagmus) and to maintain binocular vision (alphabetic syndromes, oculomotor palsy, restriction syndromes). Different causes of child vicious attitude of the head were studied in our department, oculo‐orbital diseases are not the only causes. Torticollis is a real syndrome which can be observed in various pathologies (oculo‐orbital, orthopedic, neurological and oto‐rhino‐laryngological) that ophthalmologist must not ignore. child vicious attitude of the head requires an interdisciplinary etiological investigation before any treatment.
Idiopathic intracranial hypertension secondary to iron‐deficiency anaemia
Authors: Murphy Neil , Stewart Stephen , Hrabovsky Monica
Published: January 2022

Purpose

To present a case of idiopathic intracranial hypertension (IIH) in a 21‐year‐old female patient in whom iron‐deficiency anaemia was the primary risk factor.

Methods

Case report and review of the scientific literature.

Results

A 21‐year‐old female presented to eye casualty with a 3‐day history of intermittent blurring of vision in both eyes. She denied any significant headache. Visual acuity was 6/6 in both eyes, colour vision was normal and there was no RAPD. However, dilated fundal examination revealed bilateral optic disc oedema. A CT scan of brain/orbits demonstrated a partially empty sella and mild vertical tortuosity of the optic nerves. A lumbar puncture was performed and the CSF opening pressure was elevated at 30cmH2O. These findings were consistent with a diagnosis of IIH. The patient lacked common risk factors for IIH: her body mass index was not elevated and she had not previously been prescribed tetracycline antibiotics, hormonal contraceptives or high‐dose vitamin A derivatives. However, she did have a history of excessive consumption of the oral analgesic Nurofen Plus (ibuprofen plus codeine). This had caused profound iron‐deficiency anaemia and her haemoglobin level two weeks prior to this presentation was 71 g/L. A review of the literature found three retrospective studies that examined the role of anaemia in IIH. While one study did not find any statistically significant associated between anaemia and IIH, two found that treating anaemia is associated with a faster recovery and better prognosis in patients with IIH. Correction of anaemia alone can lead to resolution of IIH.

Conclusions

Idiopathic intracranial hypertension is a complex condition and the most important neurological manifestation is papilloedema, which may lead to progressive optic atrophy and visual loss. Anaemia appears to be a risk factor for IIH and a full blood count should be included in the routine investigation of these patients.
Long‐term experience of one‐day stereotactic irradiation in patients with uveal melanoma
Authors: Furdova Alena , Sramka Miron , Smolkova Bozena , Furda Robert , Jurenova Denisa , Plesnikova Paulina , Lyskova Darina
Published: January 2022

Purpose

Uveal melanoma (iris, ciliary body, choroid) is the most frequent intraocular malignant tumor in adults. One day session stereotactic radiosurgery (SRS) with 35.0 Gy is one of current treatment options. Radiation complications can lead to visual acuity reduction or secondary enucleation of the eye globe. Radiation‐induced optic neuropathy (RION) is a severe ocular complication developing in high‐risk patients with uveal melanoma after SRS.

Methods

Long‐term analysis of 210 patients with intraocular uveal melanoma treated by SRS at linear accelerator LINAC in Slovakia by ‘One‐day session’ method: we analyzed association between the secondary enucleation and the presence of secondary glaucoma as well as the radiation‐induced optic neuropathy after SRS.

Results

The median tumor volume at baseline was 0.3cm3 with range from 0.1 to 2.7 cm3. The therapeutic dose was 35.0Gy by 99% of DVH (dose volume histogram). Average overall survival after stereotactic irradiation was 1st year after SRS 95%, 2nd year 81%, in 5 years 80%.

Secondary enucleation was necessary 17% patients due to secondary glaucoma. The presence of RION was significantly associated with a higher dose on the optic nerve (p = 0.0122 in invariable and 0.0039 in multivariable analysis, respectively). Importantly, the overall survival of patients who underwent secondary enucleation was not different from the survival of patients without enucleation (p = 0.691).

Conclusions

Survival rates at 5‐year interval and percentage of secondary enucleation due to complications after one‐day session linear accelerator irradiation are comparable to those achieved with other irradiation techniques (brachytherapy, proton beam irradiation).
Decreased glucose metabolism and glutamine synthesis in the retina of a transgenic mouse model of Alzheimer’s disease
Authors: Tams Anna Luna Mølgaard , Morello Berta Sanz , Westi Emil Winther , Mouhammad Zaynab Ahmad , Andersen Jens Velde , Freude Kristine Karla , Vohra Rupali , Hannibal Jens , Aldana Blanca Irene , Kolko Miriam
Published: January 2022

Purpose

Visual changes are some of the earliest symptoms that patients with Alzheimer’s disease (AD) experience1. Pathophysiological processes such as amyloid‐β plaque formation, vascular changes, neuroinflammation, and loss of retinal ganglion cells (RGCs) have been detected in the retina of AD patients and animal models1. However, little is known about the molecular processes that underlie retinal neurodegeneration in AD. The cellular architecture and constant sensory activity of the retina impose high metabolic demands2. We thus hypothesized that energy metabolism might be compromised in the AD retina similarly to what has been observed in the AD brain3.

Methods/ Results

To address this question, we explored cellular alterations and retinal metabolic activity in the 5xFAD mouse model of AD. We used 8‐months old female 5xFAD mice, in which the AD‐related pathology has been shown to be apparent. We observed that RGC density is selectively affected in the retina of 5xFAD mice. To map retinal metabolic activity, we incubated isolated retinal tissue with [U‐13C]glucose and analyzed tissue extracts by gas chromatography‐mass spectrometry. We found that the retinas of 5xFAD mice exhibit glucose hypometabolism. Moreover, we detected decreased glutamine synthesis in 5xFAD retinas but no changes in the expression of markers of Müller glia, the main glial cell type responsible for glutamate uptake and glutamine synthesis in the retina.

Conclusions

These findings suggest that AD presents with metabolic alterations not only in the brain but also in the retina that may be detrimental to RGC activity and survival, potentially leading to the visual impairments that AD patients suffer.

Chiquita, S. et al. The Retina as a Window or Mirror of the Brain Changes Detected in Alzheimer’s Disease: Critical Aspects to Unravel. Molecular Neurobiology vol. 56 5416–5435 (2019).

Oesch, N. W., Wade Kothmann, W. & Diamond, J. S. Illuminating synapses and circuitry in the retina. Current Opinion in Neurobiology vol. 21 238–244 (2011).

Andersen, J. V. et al. Deficient astrocyte metabolism impairs glutamine synthesis and neurotransmitter homeostasis in a mouse model of Alzheimer’s disease. Neurobiol. Dis. 148, (2021).
Distribution of proteins in the different parts of the schirmer strips
Authors: Arslan Murat Akkurt , Kolman Ioannis , Chardonnet Solenne , Pionneau Cédric , Magny Romain , Baudouin Christophe , Brignole‐Baudouin Françoise , Kessal Karima
Published: January 2022

Astract

Purpose

To analyze and compare protein composition in different parts of the Schirmer strips (called the bulb and the rest of the strip) by using a comprehensive proteomics approach based on highly sensitive trapped ion‐mobility spectrometry coupled quadrupole time‐of‐flight (timsTOF Pro).

Methods

Schirmer strips were collected from healthy subjects on 4 different visits over two consecutive days to rationally prepare three groups: 4 whole strips, 4 bulbs and 4 rests of the strips. Each group was extracted in ammonium bicarbonate before analysis with nanoElute UHPLC (ultra‐high‐pressure liquid chromatography) coupled timsTOF Pro. Protein Gene Ontology classification was performed by using Panther. Mass spectrometry data were processed using MaxQuant for protein identification.

Results

The number of identified proteins increased by 49.6% when the bulbs are separated from the rests of the strips, each group being processed independently. Most of the identified proteins (%50.5) were common in the bulbs and the rests, 26.3% identified only in the bulbs and 23.2% only in the rests. Among all, 1650 proteins were identified from three groups, binding (44%) and catalytic activities (38.3%) constituted the main groups of molecular functions. The cellular (31.3%), metabolic (20.9%), biological regulation processes (13%) formed the main classes in the biological processes of identified proteins. A high number of enzymes (480), formed of hydrolases (47.5%), oxidoreductases (22.1%), transferases (16.7%), ligases (10%), isomerases, (2.1%) and lyases (1.7%) were identified in tear proteome.

Conclusions

The separate study of the bulbs and the rests identified several proteins that are not found in the entire strip alone. Probably, treating bulbs and rests apart allowed to elute more proteins from each part. A decrease in the concentration of abundant tear proteins might have enabled the identification of less abundant ones too. This methodology could improve the pre‐analytical steps before MS analysis. The dataset created can help to model and compare multiple signaling pathways associated with ocular surface pathologies. Moreover, the TimsTOF Pro could also add a technical improvement for the investigation of biomarkers in ocular diseases.
Objectively measured rheological patterns in artificial tears
Authors: Blasco‐Martinez Alejandro , Mateo‐Otobia Antonio , Del‐Prado‐Sanz Eduardo , Blasco‐Alberto Javier
Published: January 2022

Purpose

To analyze the rheological behaviours of several artificial tears.

Methods

In vitro viscosity profile of the different artificial tears was obtained. A cone‐plate rotational rheometer was used with ascending and descending shear rate (from 1 s‐1 to 1000 s‐1, 330 measurements) at a constant temperature of 30°C and a fluid volume of 5 ml. The difference between viscosities in each section of shear rate was calculated.

Results

Four different rheological patterns were found in 78 artificial tears: shear‐thinning, shear‐thickening, thixotropic and Newtonian. Thixotropy was found between 0.17 and 104.576 mPas. Shear‐thinning, shear‐thickening and Newtonian behaviours showed a variation in viscosity in the last measurement section between −1.22 and 517 mPas.

Discussion

The viscosity of artificial tears always depends on the shear rate. It is possible to find two patterns simultaneously depending on the shear rate. These rheological patterns could serve to optimize the treatment with lubricants in different conditions of the ocular surface.

Conclusions

The variation of the shear rate conditions the viscous behavior of the fluids. We have defined four possible rheological models in the measured artificial tears. In vivo studies are necessary to evaluate the clinical utility of these findings.

Bibliography

Bhushan B. Introduction To Tribology. 2nd ed. New York: John Wiley & Sons, Inc; 2013. 711 p.

Simmons PA, Aragona P, Wang H, Wang T. Physiochemical Properties of Hyaluronic Acid‐based Eye Drops. Montpellier, France; 2016.

Lievens C, Berdy G, Douglass D, Montaquila S, Lin H, Simmons P, et al. Evaluation of an enhanced viscosity artificial tear for moderate to severe dry eye disease: A multicenter, double‐masked, randomized 30‐day study. Contact Lens Anterior Eye. 2019;42(4):443–9.

Pult H, Tosatti SGP, Spencer ND, Asfour JM, Ebenhoch M, Murphy PJ. Spontaneous Blinking from a Tribological Viewpoint. Ocul Surf. 2015;13(3):236–49.
Ocular vascular changes in relatives at high genetic risk for developing Alzheimer’s disease: foveal avascular zone and choroidal thickness
Authors: López‐Cuenca Inés , Salobrar‐Garcia Elena , Alcántara‐Rey Celia , Elvira‐Hurtado Lorena , Fernández‐Albarral José A. , Rojas P. , Isabel Ramirez Ana , Salazar J.J. , Barabash Ana , Manuel Ramirez Jose , de Hoz Rosa
Published: January 2022

Purpose

Alzheimer’s disease is the most common cause of dementia. In addition to the age,a family history (FH+) of AD and ɛ4 allele of the ApoE gene are the main genetic risk factors for developing the disease. However, ɛ4 allele of ApoE plays a protective role in age‐related macular degeneration. In both pathologies vascular changes have been reported in the retina and the choroid. The aim of this study was analyzed ocular vascular changes in subject with high genetic risks for developing AD.

Methods

A complete eye examination was carried out in 184 cognitively healthy subjects. We analyzed the choroidal thickness using optical coherence tomography (OCT) and the foveal avascular zone (FAZ) using OCT‐angiography (OCTA) and compared the results with ApoE gene expression, AD FH+, and the presence or absence of hard drusen (HD).

Results

Choroidal thickness was statistically significantly different (p < 0.05) in the (FH‐, ɛ4‐, HD+) group compared with: (i) both the (FH‐, ɛ4‐, HD‐) and the (FH+, ɛ4+, HD+) groups in the superior and inferior points at 1500 μm, and (ii) the (FH+, ɛ4‐, HD+) group in the superior point at 1500 μm, There were statistically significant differences (p < 0.05) in the superficial FAZ between the (FH+, ɛ4‐, HD+) group and i) the (FH+, ɛ4‐, HD‐) group and ii) the (FH+, ɛ4+, HD‐) group.

Conclusions

In conclusion, ocular vascular changes have not yet been found in participants at genetic risk of developing AD; however, subjects without genetic risk of AD who have HD should be followed for their evolution.
Management and follow‐up of secondary unlikely location of Dexamethasone Implant: between sulcus 3‐pieces IOL and intact posterior capsule
Authors: Youssof David , Gain Philippe , Thuret Gilles , Garcin Thibaud
Published: January 2022

Purpose

Management and follow‐up of secondary unlikely location of Dexamethasone Implant: between sulcus 3‐pieces IOL and intact posterior capsule.

Methods

A 66‐year‐old man had a traumatism while cutting wood: he consulted 3 days later for severe endophthalmitis. A CT scan excluded any metallic intraocular foreign body (FB). Initial emergency surgery consisted in phacovitrectomy without implantation, bacteriologic and fungal samples, removal of small wood FB, antibiotic & antifungal intravitreal injections. No zonulolysis was present, no capsular tear occurred. Local and systemic treatment allowed good anatomic recovery. At 1.5‐month he developed Irvine‐Gass syndrome (CME).

At 2‐months, conditions allowed secondary implantation with a 3‐pieces IOL in the sulcus due to anterior and posterior capsules fusion. As zonule and lens bag were well preserved, we injected intravitreal DI without adverse event (free in the posterior segment). Forty days after DI injection, he consulted in emergency for a hay straw in his left eye. Actually, the DI migrated to the anterior segment, just between sulcus IOL and intact posterior capsule. He had no pain, no redness, normal IOP, 0.2 logMAR far & near vision, and an impression of a paracentral scotoma. He reported repeated heavy loads lifting with head down in his farm, despite postoperative instructions. Medical treatment based on myotics (isotpopilocarpine), continuation of anti‐inflammatory drops, and prophylactic hypotonizing monotherapy drops associated with monthly complete monitoring (slit lamp/OCT/specular microscopy) was decided in first line‐therapy.

Results

Spontaneous disintegration of this ectopic DI took 2 months: CME disappeared completely in 1.5 month; IOL remained stable; no IOP elevation or endothelial damage occurred; vision went to 0.0 logMAR and paracentral scotoma disappeared.

Conclusions

This ectopic migration leading to DI sandwich enables good healing from a CME. Various options could have been chosen: among YAG capsulotomy, emergency surgery and medical treatment. Here, rigorous monitoring with precise iconographic sequences allows to estimate efficacy, safety and time of resorption in this unlikely location. DI injection should be really discussed for every trauma background.
SLC38A8 mutation spectrum in foveal hypoplasia
Authors: Derar Mohammed , Lord Emma C. , Poulter James A. , Webster Andrew R. , Bell Sandra M. , Inglehearn Chris F. , Toomes Carmel
Published: January 2022

Purpose

Significant phenotypic overlap exists between ocular albinism and SLC38A8 related foveal hypoplasia (FH) which hinders differential diagnosis. To facilitate molecular testing, we catalogued the spectrum of known pathogenic variants in SLC38A8 responsible for FH.

Methods

The UK 100 000 genomes (100KG) datasets were analysed to detect pathogenic SLC38A8 variants compatible with recessive inheritance in cases with phenotypes reminiscent of FH. Published literature was accessed to capture deleterious variants reported in FH affected families. Additional variants identified locally were incorporated for bioinformatic analysis. Variant interpretation included in‐silico pathogenicity assessment, population data and protein modelling.

Results

In total, 41 pathogenic variants in SLC38A8 have been identified in 51 FH families; 17 missense, 4 splice site, 2 in‐frame deletions, 6 frameshift, 6 nonsense, 4 large deletions, a multiple exon inversion and a whole gene deletion. Nonsense variants are evenly distributed throughout the gene and protein, while missense variants are more likely to reside in transmembrane domains. 38 SLC38A8 variants were reported in the literature and we have identified 3 novel and 2 known variants in 4 families derived from the 100KG datasets and our local cohort. In one patient, a novel g.84049578_84060679inv (GRCh37) was detected in a homozygous state. Another harboured novel variant c.922_923insTG, p.(Thr308Metfs*14) and c.922A>G, p.(Thr308Ala). Other homozygous variants include c.848A>C, p.(Asp283Ala) and novel variant c.77C>T, p.(Ser26leu). Protein modelling of SLC38A8 predicted a destabilising effect by both p.(Ser26leu) and p.(Thr308Ala). Haplotype analysis of Pakistani, Bangladeshi and Indian patients harbouring c.264C>G, p.(Tyr88*) suggest a South Asian founder effect.

Conclusions

We reviewed and extended the spectrum of SLC38A8 variants causative for FH. The presence of multiple nonsense variants and in‐silico modelling of missense variants suggests a complete loss of function as the likely disease mechanism.
Intraperitoneal administration of lipopolysaccharide (LPS) causes retinal ganglion cell loss in mice
Authors: Tatiana Rodríguez Ramírez Kristy , Vidal‐Sanz Manuel , Agudo‐Barriuso Marta
Published: January 2022

Purpose

To analyze the effect of a systemic inflammatory insult induced by LPS administration on retinal ganglion cells and on microglial activation in female and male mice.

Methods

Female and male C57BL/6J mice were treated with a single intraperitoneal injection of LPS (5mg/kg). As control intact animals were used. At 3, 7 and 15 days after LPS administration, retinas were dissected as flat mounts and Iba1 (microglia) and Brn3a (RGCs) immunodetected.

Results

Microglial activation was observed at 3 days and was qualitatively similar in both sexes. RGC loss was observed at 3 days (p < 0.0001 compared to intact retinas) and was significantly lower in females (13% loss of the original RGC population) than in males (20%). In both sexes, RGC loss progressed until day 7 reaching 28% in females and 34% in males. From 7 to 15 days there was not further loss of RGCs.

Conclusions

One single injection of LPS causes microglial activation and neuronal death that is higher in males than females.