bluuebunny/crossref_metadata_2025 huggingface dataset:
Cellular remodelling of the inner retina and the retinal ganglion cells in experimental retinal detachment
Authors: Tsoka Pavlina , Steirou Theodora , Tsilimbaris Miltiadis K.
Published: December 2022

Purpose: Anatomical surgical outcomes for the treatment of retinal detachment (RD) are outstanding; however, only 50% of the patients with a detached macula regain 5/10 or better vision. Thus, to preserve or restore visual function in RD, several gaps in our understanding of the pathophysiology of the disease need to be bridged. Therefore, the purpose of the current study, was to investigate the anatomical/morphological changes of retinal interneurons and retinal ganglion cells (RGCs) in an experimental model of RD.

Methods: Experimental RD was induced in C57BL6/J mice by a subretinal injection of 1% sodium hyaluronate. Following RD, mice were euthanized at 1‐, 3‐, 7‐, 30‐ and 90‐days post‐surgery and eyes or retinas were isolated and proceed for sectioning or retinal whole mounts respectively. Immunofluorescence and electron microscopy studies were performed against protein kinase C alpha (PKC‐α) to target rod bipolar cells, calretinin and calbindin D to target horizontal cells and brain‐specific homeobox/POU domain protein 3A (Brn3a) and neuron‐specific class III beta‐tubulin (β‐tubulin III) to target RGCs.

Results: Three days post‐RD, PKC‐α+ neurons (rod bipolar cells) began to migrate towards the outer nuclear layer (ONL), while 30 days post‐RD they had significantly migrated towards the ONL and displayed irregular distribution of their cell bodies in the inner nuclear layer. Similarly, processes of horizontal cells also migrated towards the ONL, 7 days post‐RD and became more invasive and disoriented after longer‐term detachment (30 days post‐surgery). Moreover, there was a significant increase in the intensity of calbindin D, 30‐days post‐RD. Brn3a/β‐tubulin ΙΙΙ+ RGCs were significantly fewer 30‐ and 90‐days post RD. All retinal neurons that were examined, did not show any noteworthy differences 1 day post RD.

Conclusions: RD resulted in significant anatomical changes in both rod bipolar and horizontal neurons of the retina along with a notable reduction of RGCs. The cellular response of the inner retina and the RGCs of the detached retina might play an important role in the imperfect visual score of an anatomical successful surgical reattachment.
The prevalence of cataract by vision screening in a Belgium nursing home residents in 2021
Authors: Moghaddam Zahra Javdani Sanatgar
Published: December 2022

Purpose: With an ageing population that continues to grow, and 13.6% of the population aged 65 or over receive long term formal care, 8.5% residing in Elderly homes in Belgium. We aim to map prevalence of visual impairement, and blindness caused by cataract, and refractive errors in a nursing home in Belgium.

Methods: Between 07/04/2021 and 09/05/2021, 170 residents of a nursing home in Flanders were examined. Detailed medical and family history, complete ophthalmological examination including visual acuity, slit lamp examination of the anterior segment of the eye, measurement of intraocular pressure, eye fundoscopy and OCT (not in all of them) was performed.

Results: Visual acuity of 146 residents (88%) of 170 residents of elderly home, 111 (65.29%) women and 59 (34.70%) men was determined. Mean age of the residents was 81.54 (±10.89) years. Of all participants, 8 (4.70%) were blind and 63 (37.06%) were moderately or severely visually impaired. In 24 residents (14.12%), visual acuity could not be determined. The prevalence of cataracts, secondary cataract and previous cataract surgery in the 170 residents was: respectively 102(60.00%), 27 (15.88%) and 36 (21.80%).

In the 102 residents with cataracts, secondary cataracts and operated of cataract were respectively 90 (52.94%), 15 (%) and 32 (%) bilateral and 12 (%), 12 (7.06%) and 4 (%) unilateral.

Conclusions: Many elderlies in these nursing home have poor access to Eyecare, because of their immobility. This might lead to vision impairment and blindness, affecting their social life and quality of life. An ophthalmological examination and treatment can be useful to avoid progressive visual impairment and eventually blindness.

Author Javdani Sanatgar Moghaddam Zahra, MD, (Presenting Author) irisjavdani@yahoo.fr

Other Authors.

Prof Robert Kuijpers robert.kuijpers@uzbrussel.be

Dr Frank Goes frank@goes.be
Autophagy protects retinal pigment epithelial cells from hydroquinone‐induced toxicity
Authors: Hytti Maria , Kauppinen Anu , Kaarniranta Kai
Published: December 2022

Purpose: Age‐related macular degeneration (AMD) is a complex disease and the most common cause of blindness among the elderly in the Western world. Dysfunctional cellular clearance and increased oxidative stress are known to play a role in retinal pigment epithelial (RPE) cell death and dysfunction, which secondarily leads to photoreceptor degeneration and a loss of central vision. Smoking, which increases oxidative stress on a cellular level is a known risk factor for AMD. Here we assess the role of autophagy in the survival of ARPE‐19 cells exposed to the cigarette smoke component hydroquinone and in the secretion of the vascular endothelial growth factor (VEGF).

Methods: We exposed ARPE‐19 cells to 100 μM hydroquinone following either 1 h or 24 h of serum‐starvation, which induced autophagic clearance. At the same time, autophagy was inhibited either at the early or the late stage using 3‐Methyladenine or bafilomycin A1, respectively. Cytotoxicity was assessed using the lactate dehydrogenase (LDH) or the MTT assay. VEGF secretion was measured from the medium using ELISA.

Results: Hydroquinone exposure reduced cell viability to 50% of control when hydroquinone was added following a 1 h serum starvation. Inversely, if cells were starved for 24 h prior to hydroquinone exposure, no toxicity was observed. Inhibition of autophagy at the early but not the late stage significantly reduced the survival of cells starved for 24 h prior to hydroquinone exposure. At the same time, autophagy inhibition significantly reduced VEGF secretion to the medium.

Conclusions: Autophagy activation effectively prevented oxidative stress‐induced cytotoxicity in RPE cells, highlighting the importance of functional autophagy in RPE cells and in the prevention of AMD.
miRNAs regulating gene expression/gene networks and its multifactorial pathways in open‐angle glaucoma
Authors: Blasco Irene Andrés , Raga‐Cervera Jorge , Bolarin Jose M. , Gallego‐Martinez Alex , Sánchez Javier Benítez‐Del‐Castillo , Pinazo‐Durán Maria D. , Zanón‐Moreno Vicente
Published: December 2022

Purpose: To describe the microRNAs (miRNAs) involved in ocular hypertension (OHT) and open‐angle glaucoma (OAG) to develop miRNA‐based glaucoma diagnostic and therapeutic tools.

Methods: An analytical, observational, case–control study was performed in 42 volunteers of both sexes, aged 50 to 80 years, that were classified according to: suffering OHT (n = 20) or with the diagnosis of OAG (n = 20). All participants were interviewed for obtaining sociodemographic and personal/familial records, ophthalmologically examined, and their tear samples were collected and frozen at 80 °C until processing for molecular‐genetic assays. Tear RNA extraction, libraries construction, and next generation sequencing were performed. In addition, Gene information was set up from the DIANA‐TarBase v7, DIANA‐microT‐CDS, and TargetScan v7.1 databases. To build a network of metabolic pathways, only genes appearing in at least four of the following databases: DisGeNet, GeneDistiller, MalaCards, OMIM PCAN, UniProt, and GO were considered.

Results: Mean age of participants was 61.1 ± 2.4 years (OHT subjects) and 64.5 ± 1.4 years (OAG patients). In this work we have investigated the delivering of intact miRNAs to target tissues by analysing the tear samples. We identified 95 miRNAs in tears of the OHT subjects and/or OAG patients. When comparing tears from both study groups, the differential expression profiling of eight miRNAs: miR‐26b‐5p, miR‐152‐3p, miR‐30 e‐5p, miR‐125b‐2‐5p, miR‐224‐5p, miR‐151a‐3p, miR‐1307‐3p, and miR‐27a‐3p was found. Also, the interaction networks of the above miRNAS were identified in HTO versus OAG.

Conclusions: We propose specific miRNAs and their target genes/signalling pathways as candidates for a better understanding of the molecular‐genetic bases of OAG.
Improvement of hydroxychloroquine retinopathy monitoring by informatic systems
Authors: Alacid Alberto López , Franco Pedro Esteban Quílez , de Imperial Ollero Juan Antonio Miralles , Jiménez Andres López
Published: December 2022

Purpose: To study the proportion of patients treated with hydroxychloroquine in Health Area VII of Murcia following the screening recommended by the international guidelines and to implement a system to improve the screening efficacy.

Methods: We studied the patients in Health Area VII of Murcia, Spain, treated with hydroxychloroquine between January and November 2019 to find out whether patients were correctly screened for retinopathy. Demographic data, medical specialty prescribing hydroxychloroquine, disease, year of onset and examinations performed in our Ophthalmology Service were collected.

Results: A total of 202 medical records were reviewed. Baseline ophthalmologic exams were performed in 63.9% of cases: fundus examination (96.9%) and optical coherence tomography (OCT) (33.3%). Follow‐up examination was performed in 61.8% of cases. Follow‐up was complete, with OCT, 10‐2 visual field and autofluorescence image in only 2.4% of patients. The time between revisions was 1.6 years on average. These results strongly deviated from the guidelines. We planned a strategy to improve the screening of these patients. We developed a computer database that allows the voluntary and automatic registration of patients treated with hydroxychloroquine, including contact and demographic data, start date of treatment, the daily dose and retinopathy risk factors. With this database, the patient's appointment in ophthalmology will be provided with the corresponding tests. The examination will be assessed by telemedicine and the time of the next check‐up will be determined according to the results.

Conclusions: This plan aims to capture most patients starting the treatment with hydroxychloroquine and to carry out the appropriate tests at each visit with strict follow‐up, thus reducing the care load.

References

1. Yusuf IH et al. Eye (Lond). Hydroxychloroquine and Chloroquine Retinopathy: Recommendations on Monitoring, 2021 Jun; 35(6):1532–1537.
Microglial alterations as a possible treatment target in retinitis pigmentosa
Authors: Almansa Inmaculada , Sanz María Miranda , Sánchez‐fideli Amparo , Trull Carmen
Published: December 2022

Purpose: The term retinitis pigmentosa (RP) describes a group of hereditary retinopathies. The first clinical signs of RP are night blindness and loss of peripheral vision. Central vision remains preserved until advanced stages of the disease. At a cellular level, the rods are the first to degenerate. Subsequently, there is degeneration of the cones. Inflammation plays a fundamental role in RP. The microglia respond quickly to alterations, acquiring amoeboid morphology; migrating to damage focus; acquiring macrophages functions; phagocytosing cellular debris; secreting molecules that initiate tissue repair; and favouring neuroprotection. However, if the activation is excessive, the constant secretion of nitric oxide and proinflammatory cytokines lead to pathological side effects. The purpose of this work was to review published studies in order to know if the inhibition of micloglial activation may be a good option to increase photoreceptor protection.

Methods: A systematic literature review was conducted, in accordance with PRISMA criteria, in different bibliographic databases: Medline, Embase, SCOPUS and Web of Science. We searched human and animal reviews, published in English in the past 10 years. Initial search terms were ‘retina’, ‘retinitis pigmentosa’, ‘retinal degeneration’ and ‘therapeutics. Duplicate studies were removed, and the remaining articles were assessed for eligibility by full‐text review.

Results: Understanding the mechanisms leading to photoreceptor death is essential for the development of new treatments in RP. It has been shown increased retinal infiltration of activated microglia in many animal models of RP. Different works have studied the clinical efficacy of antioxidants, minocycline, transforming growth factor beta or tamoxifen. However, the complete efficacy in RP has not been fully established.

Conclusions: Pharmacological inhibition of microglial activation may be a good therapeutic target to reduce photoreceptor cell death in RP.
Tear metabolomics. An outstanding approach to the molecular diagnosis of glaucoma
Authors: Gallego‐Martinez Alex , Martinez‐Bisbal Mari Carmen , Andres‐Blasco Irene , Marabotto Marina Dolores Botello , Hernandez‐Martinez Francisco Javier , Martinez‐Mañez Ramon , Duran Maria Dolores Pinazo
Published: December 2022

Purpose: The open‐angle glaucoma (OAG) is the first cause of irreversible blindness worldwide, being the main risk factor the elevated intraocular pressure (IOP). The molecular mechanisms of OAG development and progression remains incomplete. Because of this, biomarkers for early diagnosis of OAG are not conclusive. We deal with understanding the metabolomics of OAG by using 1H‐ nuclear magnetic resonance (NMR) spectroscopy in tear samples for searching specific metabolites that improve early molecular diagnosis of OAG.

Methods: 1H NMR monodimensional experiments were acquired from tears in 30 tear samples (OAG patients: n = 11 and healthy controls: n = 19). Additionally, 2D (TOCSY and 1H‐13C HSQC) experiments were acquired in a reduced set of samples to assign the resonances. Spectra underwent phase, baseline and chemical shift correction. The signals in the spectra were assigned, integrated and normalized to the total sum of integrals. Finally, data were analysed by multivariate statistics (PLS‐DA) to determine a model to discriminate between the controls and OAG tears. The whole data set was split into calibration (18 samples) to calculate the model and validation set (10 samples) to test the performance and the ability for disease discrimination.

Results: The calculated PLS‐DA model showed a sensitivity of 100% and a specificity of 83.3% to discriminate OAG patient's tears versus control tears in the validation set. The set of metabolites participating is this discriminant model were obtained, mainly those involved in specific cellular and molecular pathways regarding the pathologic mechanisms of OAG.

Conclusions: Data obtained by 1H‐NMR spectroscopy in tears confirms the validity of metabolomics as a non‐invasive approach to better OAG managing.
The use of anterior segment optical coherence tomography in infectious keratitis
Authors: Hassairi Asma , Jendoubi Fahd , Fendouli Ines , Limaiem Rim , El Matri Leila
Published: December 2022

Purpose: To describe the anterior segment optical coherence tomography (AS OCT) findings in infectious keratitis.

Methods: Forty‐five patients with confirmed microbial keratitis were included in this prospective, observational case series study. All subjects underwent ophthalmologic examination. AS OCT scanning was performed on presentation and at follow‐up.

Results: 25 patients (55%) had microbial keratitis, 18 patients (40%) had herpetic keratitis and Two patients (4%) had Fungal keratitis. Twelve different patterns were identified. Thirty‐two of the 45 eyes (71%) had epithelial defect associated with sub‐epithelial infiltrates in twenty cases (44%). In 13 of these cases, hydropic changes were observed. Thirty‐six eyes (80%) showed stromal involvement. Stromal infiltrates were also seen, in twenty cases, as a diffuse or local hyper‐reflective area. Five cases (11%) were associated with uveitis: Retrocorneal hyperreflective deposits, thick inflammatory plaque attached to the endothelium and anterior chamber inflammatory cells were imaged.

Conclusions: Infectious keratitis has characteristic features on AS‐OCT images. These patterns are not specific and do not orient towards the nature of the microorganisms but AS‐OCT imaging may provide useful supplementary information for diagnosing and monitoring infectious keratitis.
Glaucoma detected as minimal cross section of the nerve fibre layer at the ONH, average thickness provides comparable specificity to integrated area when comparing subjects
Authors: Soderberg Per , Yu Zhaohua , Kisonaite Konstancija
Published: December 2022

Purpose: To determine if integrated area provides better specificity than average thickness for measurements of minimal cross‐section of the nerve fibre layer at the optic nerve head (ONH).

Methods: In each of 40 non glaucomatous subjects aged 20–69 years, male/female ratio 1, the ONH was captured in 3D with Topcon OCT‐Triton with a raster scan. Subjects were recruited stratified to provide even age distribution. The ONH volumes were exported and the minimal cross‐section of the nerve fibre layer at the ONH was segmented fully automated with a custom algorithm. The minimal cross‐section around the circumference of the ONH was for half the sample estimated as average thickness (μm), PIMD‐2Pi, and for the other half as integrated area, PIMA‐2Pi (mm2). For each sample, the dependence on the estimates on age was fitted to a straight line with linear regression, providing the quantity at average age and the age loss for each quantity. Then, for each quantity, the specificity for level at average age and age loss was estimated numerically as a 95% confidence interval considering a threshold for not pathological of 0.1 of the estimated mean above the mean. Further, the difference in specificity between the two quantities was numerically estimated as a 95% confidence interval for the difference between specificities for the two quantities.

Results: The specificity for not pathological was for; PIMD‐2π:average age, [0.67;0.80], PIMA‐2π:average age, [0.68; 0.82] (d.f. = 18), difference average at age, [−0.09; 0.11] (d.f. = 36), PIMD‐2π: thickness·year−1, [0.39; 0.45], PIMA‐2π: area·year−1, [0.36; 0.43] (d.f = 18), difference year−1, [−0.07; 0.03] (d.f = 36).

Conclusions: When comparing subjects, there is no advantage of estimating the minimal cross‐section of the nerve fibre layer over the circumference of the ONH as integrated area as compared to average thickness, with regard to differentiating pathological from not pathological.
Fungal blebitis due to Aspergillu ustus. About the first case described in the literature
Authors: Díaz‐Barreda Mª. Dolores , Boned‐Murillo Ana , Pinilla Isabel , Rivasés Guillermo Pérez , Fernández Miguel Castillo , Pérez Itziar , Pardina Elena , Garcia Diana Perez , Martinez Juana , Ibañez Juan
Published: December 2022

Purpose: Blebitis is the infection of the valve created in glaucoma filtering surgery. Only 4 cases have been described that refer to ophthalmic infections caused by A. ustus, the pathogen demonstrated in the cultures in this case.

Methods: We present the case of a 73‐year‐old woman with a history of hypertension, dyslipidaemia, hyperuricaemia, hypothyroidism and glaucoma in both eyes under maximum topical treatment, despite which she had elevated intraocular pressure (IOP) and structural progression in the right eye (RE). Trabeculectomy with mitomycin‐C (MMC) was performed in RE. After 36 days, the patient came to the emergency department with a slightly painful red and secretions in RE. Examination revealed a whitish bleb, hyperfiltration, fibrin in the anterior chamber and mild corneal oedema. The vitreous was not found to be involved at any time. A conjunctival swab was taken and treatment was started and the patient was admitted for blebitis 3 days later. Two anterior vitrectomies were necessary, the first with collection of aqueous humour (AH) samples and intravitreal injection of vancomycin, the second, after 3 weeks, with phacoemulsification (leaving the patient in aphakia), collection of AH and vitreous samples and intravitreal injection of voriconazole with the addition of oral fluconazole.

Results: Eleven weeks after the first surgery Aspergilus ustus was isolated in vitreous humour samples. After 1 year of follow‐up the patient has visual acuity (VA) of light perception in RE, ptisis bulbi, hypotonia, without pain, discomfort, signs of infection or any other symptoms. Together with her it was decided to perform enucleation.

Conclusions: Blebitis is a potentially fatal complication whose risk does not decrease over the years. Being alert to warning signs and symptoms is paramount for early detection and optimal management. To our knowledge this would be the first reported case of A. ustus blebitis.
Pupilar block after cataract surgery
Authors: Martínez Marta Suñer , Alperte Juan Ibañez , Cisneros‐Arias Pablo , Claverías Julia Aramburu , Fernández Miguel Castillo , Nuñez‐Moscarda Eva , Orejudo‐Rivas Marta , Pérez‐Rivasés Guillermo , el Bakkali Ismael Bakkali , García Diana Pérez
Published: December 2022

Purpose: To describe a case of pupillary block in a pseudophakic patient secondary to synechiae between the iris and the intraocular lens implanted in the capsular bag.

Methods: 60‐year‐old woman presented severe diabetic retinopathy and cataract in her right eye. Phacoemulsification + hydrophobic monofocal intraocular lens in capsular bag was decided. The next day, we found a hemovitreous in right eye, observation was decided after performing ultrasound. As the condition did not resolve, a pars plana vitrectomy was performed. Seventeen days after the second surgery, the patient presented intense pain in her right eye, visual acuity of hand motion, IOP of 70 mm Hg, intense corneal edema, iris bombe, wide chamber and narrow in the periphery. Correct pseudophakia. Irregular pupil with mild non‐reactive miosis. Closed angle. Topical hypotensive drugs, oral acetazolamide, and IV mannitol were prescribed without response. Peripheral iridotomies were performed with good response. Mydriatics are added to force pupillary dilation.

Results: The next day she presented an IOP 10. One month after the iridotomies she presented an IOP 12 and visual acuity of 0.6.

Conclusions: Pseudophakic pupillary blocks rarely occur with current phacoemulsification techniques and capsular bag intraocular lens implantation. Complications inherent to surgery and patients (glaucoma, diabetes, children, previous early surgery) that predispose to a greater inflammatory context may be associated with the potential development of synechiae between the iris and the anterior intraocular lens / capsule, preventing the correct flow of the aqueous humour due to the pupillary block. In a study of the type of intraocular lens in a uveitic context, a greater association was found with hydrophobic intraocular lens than with other types. The ocation where the intraocular lens is implanted is also related, being greater in the intraocular lens in the anterior chamber or sulcus. Peripheral YAG laser iriditomies are a good therapeutic option but are not recommended intraoperatively because they can cause more complications than benefits.
Comparative analysis of corneal versus scleral tunnel incision implantation of anterior artisan Aphakia intraocular lens
Authors: Gonzalez Rocío Vega , Ruiz‐Medrano Jorge , Flores‐Moreno Ignacio , García‐Consuegra Pablo , Ruiz‐Moreno Jose María
Published: December 2022

Purpose: To evaluate the surgically induced astigmatism (SIA), efficacy and safety of two distinct accesses for anterior Artisan Aphakia IOL implantation in patients without capsular support.

Methods: Outcome data were collected for all patients who had undergone prepupillary Artisan Aphakia IOL insertion associated with pars plana vitrectomy from October 2016 and June 2022 at Puerta de Hierro‐Majadahonda University Hospital. All those with available preoperative and postoperative IOL master keratometry records were included in the analysis. The results were analysed by the incision type (corneal versus scleral tunnel).

Results: Ninety‐seven eyes from 79 patients were included. Average follow up was 2 years. Forty‐five (48%) were corneal incisions and 53 (52%) were scleral tunnels. The main causes were: 33 (32%) eyes with Marfan syndrome, 27 (26%) eyes had a complicated cataract surgery and 23 (23%) eyes had luxation or subluxation of the IOL‐capsule complex. The mean surgically induced astigmatism (SIA) in the scleral tunnel group (1.28 ± 1.15 diopter [D]) was significantly lower than in the corneal incision group (2.20 ± 1.27 D) (p < 0.001). The mean BCVA was better in the scleral tunnel group (0.18 ± 0.33 logMAR) than in the corneal incision group (0.27 ± 0.53 logMAR), although the difference was not significant (p = 0.09). The rate of complications did not show differences between groups. Two eyes (2%) developed corneal decompensation. There were 20 (20.67%) cases of cistoid macular edema (11 in the scleral tunnel group and 10 in the corneal incision group). In the scleral tunnel group, there was a tendency to first day postoperative hypotonia (24.5%) (p = 0.06), in all cases it resolved with conservative measures within 1 week.

Conclusions: Scleral‐incision approach is a safe technique that should be performed for anterior Artisan Aphakia IOL implantation in order to reduce SIA and improve BCVA. Intraocular pressure should be monitored throughout the first postoperative week.
lax eyelid condition and floppy eyelid syndrome prevalence in obstructive sleep apnoea syndrome patients: A systematic review and meta‐analysis
Authors: Ceccarelli Francesca , Afflitto Gabriele Gallo , Bonetti Mario Alessandri , Cesareo Massimo , Aiello Francesco , Nucci Carlo
Published: December 2022

Purpose: The aim of this systematic review and meta‐analysis was to explore the available literature to estimate the prevalence rate of lax eyelid condition (LEC) and floppy eyelid syndrome (FES) in obstructive sleep apnoea (OSA).

Methods: PRISMA guidelines were acknowledged in the conduction of this work, whose protocol has been registered in PROSPERO. Four electronic databases were searched from inception to December 24, 2020. A random intercept logistic regression model was carried out for the analysis of overall proportions, while mean difference was calculated as a measure of effect size to compare continuous variables. The estimated numbers of LEC/FES patients in OSA were calculated by multiplying the prevalence rate determined by our random‐effects model and the corresponding Benjafield's et al population prospect.1

Results: We included 11 studies comprising 1225 OSA patients of whom 431 and 153 affected by LEC and FES, respectively. Our model estimated a pooled prevalence rate for LEC and FES in OSA patients of 40.2% (95%CI: 28.6–53.1%) and of 22.4% (95% CI: 13.8–34.2%), respectively. The number of LEC/FES affected individuals among OSA patients is expected to peak up to 376 and to 210 million, respectively. OSA patients appeared to have a 3.4 (95% CI: 2.2–5.2) and a 3.0 (95% CI: 1.7–5.5) increased risk of developing LEC and FES than the healthy counterpart.

Conclusions: Given the strict association between LEC/FES and OSA both sleep physicians should consider the eventuality of ocular comorbidities in sleep apnoea patients and ophthalmologists should investigate the occurrence of sleep disturbances whenever any case of lid laxity is encountered.

Reference

1. Benjafield AV, Ayas NT, Eastwood PR, Heinzer R, Ip MSM, Morrell MJ, Nunez CM, Patel SR, Penzel T, Pepin JL, Peppard PE, Sinha S, Tufik S, Valentine K, Malhotra A. Estimation of the global prevalence and burden of obstructive sleep apnoea: a literature‐based analysis. Lancet Respir Med 2019; 7: 687–698.
Retinal vascular changes in response to hypoxia
Authors: Westwood Jessica , Simpkins Ciaran , Mayhook‐Walker India , Normando Eduardo Maria , Morris Daniel , Darby‐Smith Andrew
Published: December 2022

Purpose: Increased tortuosity and engorgement of retinal vasculature are recognized physiological responses to hypoxia. This can lead to high‐altitude retinopathy (HAR), which is a pathology seen in unacclimatised individuals at altitude. It typically features asymptomatic flame haemorrhages, but incidence reports are highly variable and our understanding of the aetiological mechanisms remains incomplete. This study aimed to evaluate retinal vascular changes throughout an expedition to 4167 metres.

Methods: 10 healthy participants summitted Mount Toubkal, Morocco. Fundus images were taken on a handheld camera pre‐departure, daily throughout the expedition, and one‐month post‐return. Diameter and tortuosity of four vessels was assessed, in addition to vessel density and the presence of HAR.

Results: Significant (p ≤ 0.05) increases in tortuosity and diameter were observed in some vessels on high‐altitude exposure days. There was a significant increase in vessel density on summit day only.

Conclusions: This is the first study to report increased vessel density and no incidence of HAR. These results are likely attributable to relatively low altitude exposure, a conservative ascent profile, and the young, healthy demographic profile of participants. However, the study is limited by its small sample size, environmental confounding factors and semi‐subjective diameter measurements. Physiological but not pathological changes were seen in this cohort, which gives insight to the state of the cerebral vasculature throughout this expedition and builds on current understanding of retinal vascular changes in hypoxia. Future work must include daily retinal images of larger sample sizes at higher altitude and take steps to mitigate against environmental confounders. This work is relevant to altitude tourists, patients with diabetic retinopathy or retinal vein occlusion, and critically ill patients at sea level.
Prevention campaign for amblyopia and other eye disorders among schoolchildren
Authors: López Carmen Miquel , Perea Juan Antonio Sánchez , Menargues Manuel Almarcha , Abellán Maria Victoria Navarro , Andreu Ester Mainar
Published: December 2022

Purpose: This is a retrospective longitudinal observational study to detect amblyopia and other visual anomalies (refraction, strabismus, pathologies…) in 3, 4 and 5‐year‐old schoolchildren. Amblyopia is a disorder of sight in which the brain fails to fully process input from one eye and over time favours the other eye. It results in decreased vision in an eye that typically appears normal in other respects. Early detection improves treatment success. There is currently an early detection program but according to a recently published study, does not have good compliance or appropriate material.

Methods: The study was carried out with children aged 4–6 years from 4 different schools, collecting 491 children with the corresponding informed consent of their parents. The study was divided into two phases, first an optometrist performed an external examination, red reflex, pupillary examination, ocular motility, cover test and photoscreening with a portable autorefractometer. And if any anomaly is detected in the second phase, it would be explored by an ophthalmologist who would also perform stereopsis tests, visual acuity, dilated refraction, eye fundus, and diagnosis and treatment.

Results: 491 children were included in this study, visual anomalies were detected in 96, of which 60 were studied in our center. It was detected 47% who had refractive problems, 5% strabismus and 0% opacities. Extrapolating it to the total number of patients seen, 9% had refractive problems and 1% strabismus.

Conclusions: Amblyopia has a prevalence of 6% in the population. Its treatment is relatively simple with glasses and patches at a low cost. There is a prevalence of 5%–7.5% of amblyopia in <6 years, 1%–3% strabismus in <6 years as well as 1 of 3 school failure is caused by visual problem.

Paediatric check‐up or other check‐ups that these schoolchildren do not detect this type of condition. Therefore, the Campaign for the Prevention of Amblyopia and Other Visual Anomalies idea should be implemented in all the Autonomous Communities.

Reference

1. Eileen E Birch. Amblyopia and binocular vision. Prog Retin Eye Res. 2013; 33: 67–84.
Repeatability of retinal thickness measurements in children using spectral domain optical coherence tomography
Authors: Boned‐Murillo Ana , Garcia Diana Perez , Diaz Maria Dolores , Cano Ana Sánchez , Remon Leon , Hospital Elvira Orduna , Fernández‐Espinosa Guisela , Pinilla Maria Sopeña , Rivasés Guillermo Pérez , Lozano Isabel Pinilla
Published: December 2022

Purpose: To evaluate the influence of age in the repeatability of retinal thickness measurements in a healthy paediatric population with spectral domain Optical Coherence Tomography (SD‐OCT). Knowledge of RNFL parameters and macular characteristics in a normal population and differences between ages and sexes is useful for evaluating normal development of the eyes. Also, an essential quality in determining the utility of a device for clinical use is its measurement variability. Repeatability is important for distinguishing normal subjects from patients with disease as well as for following ocular modifications over time for follow‐up after treatment, especially in young population.

Methods: Seventy‐six eyes from 76 healthy paediatric subjects underwent three fast macula scans and 81 eyes from 81 healthy paediatric subjects were studied by three retinal nerve fiver layer (RNFL) measurements using a Spectralis OCT device. Mean thicknesses in the nine Early Treatment Diabetic Retinopathy Study (ETDRS) and in the seven optic nerve RNFL areas were measured. Mean values were evaluated by age and by sex. Children were divided in two groups, Group 1/ 6 years old or younger and group 2/ children older than 6 years. We calculated the repeatability comparing the two age groups, looking for intraclass correlation coefficient (ICC) and coefficient of variation (COV) values.

Results: In the younger group central macular thickness value was 262.52 ± 18.28, and the central RNFL 104.03 ± 7.99. In the group of children older than 6, central macular thickness was 270.57 ± 18.49 and the central RNFL 100.27 ± 8.58. No statistically significant differences were found. Central retina thickness COVs were 7.00 in group 1% and 6.83% in Group 2. Optic disc RNFL thickness COVs were 7.72% in Group 1 and 8.69% in Group 2. All ICCs were higher than 0.8 showing excellent correlation among the three measurements performed by the same operator.

Conclusions: Repeatability of Spectralis OCTs is high in healthy macula measurements, and significantly higher with Spectralis. Small differences were found between repeatability of macular thickness measurements obtained by both devices analysed by age.
Age‐ and sex‐based evaluation of the association between refractive error and age‐related macular degeneration in the Korean population
Authors: Jee Donghyun
Published: December 2022

Purpose: The aim of this study was to investigate the association between refractive error and prevalence of age‐related macular degeneration (AMD) in Korean adults, based on the sex and age group.

Methods: This was a nationwide population‐based cross‐sectional study that included 17,676 subjects aged over 40 years who participated in the 2008–2012 Korean National Health and Nutrition Examination Survey. Digital fundus images (45°) were obtained for both eyes under physiologic mydriasis and were graded using the international classification and grading system for age‐related macular degeneration. The spherical equivalents of refractive errors were calculated in diopters using auto‐refraction data.

Results: After adjustment for potential confounders, myopia was associated with lower risk of any age‐related macular degeneration [odds ratio (OR), 0.74; 95% Confidence Interval (CI), 0.61–0.91]. In particular, myopia was significantly associated with lower odds of age‐related macular degeneration in female participants (any AMD: OR, 0.71; 95% CI, 0.54–0.93; early AMD: OR, 0.70; 95% CI, 0.53–0.93) and in participants younger than 50 years (any AMD: OR, 0.46; 95% CI, 0.24–0.90; early AMD: OR, 0.47; 95% CI, 0.24–0.93). There was no significant association between myopia and age‐related macular degeneration in male participants and in participants older than 50 years.

Conclusions: In the Korean adult population, myopia was associated with significantly lower odds of any type of early age‐related macular degeneration, particularly in females and in younger age groups.
Impairment of amacrine starburst cells and their synaptic contacts with dopaminergic cells could explain motion perception disturbances in Parkinson's disease
Authors: Saez Xavier Sanchez , Ortuno‐Lizaran Isabel , Castillo Carla Sánchez , Vidal‐Gil Lorena , Maneu Victoria , Lax Pedro , Cuenca Nicolas
Published: December 2022

Purpose: Parkinson's disease (PD) patients suffer from visual deficiencies in the early stages of the disease. One of these visual symptoms is the impairment of the motion perception. In that sense, we wanted to determine if the starburst amacrine cells (the main cell type involved in motion perception) are degenerated in PD. Also, we sought to evaluate if this possible degeneration is related to the degeneration of the dopaminergic system.

Methods: Post‐mortem human eyes from control and PD donors were used in this study. Immunohistochemistry and confocal microscopy were used in whole‐mount retinas to evaluate tyrosine hydroxylase‐positive cell density (dopaminergic amacrine cells), and choline acetyltransferase‐positive cell density (starburst amacrine cell). Moreover, we quantified the dopaminergic synaptic contacts with starburst amacrine cells using vesicular monoamine transporter‐2 (VMAT2) antibodies.

Results: There is a decrease in the dopaminergic amacrine cell density in PD retinas. Furthermore, we found a decrease in the number of starburst amacrine cells. Importantly, we describe for the first time that dopaminergic amacrine cells contact with starburst amacrine cells in the retina and that these connections decrease in PD patients.

Conclusions: This work shows the degeneration of starburst amacrine cells and their synaptic connections with dopaminergic cells, and this may explain the disturbances in motion perception present in PD. Importantly, these deficiencies can be used as a biomarker of this pathology performing functional tests for visual motion perception.

Support: Ministerio de Ciencia e Innovación (FEDER‐ PID2019‐106230RB‐I00). Ministerio de Universidades (FPU16/04114). Instituto Carlos III (RETICS‐FEDER RD16/0008/0016). Generalitat Valenciana (IDIFEDER/2017/064, ACIF/2020/203). Michael J Fox Foundation for Parkinson's Research.
The ROCK‐inhibitor ripasudil suppresses the expression of extracellular matrix proteins in Fuchs endothelial corneal dystrophy
Authors: Strunz Maria , Zenkel Matthias , Schlötzer‐Schrehardt Ursula , Kruse Friedrich
Published: December 2022

Purpose: Fuchs endothelial corneal dystrophy (FECD) is characterized by a progressive loss of human corneal endothelial cells (HCEC) and excess deposition of extracellular matrix (ECM). As FECD pathophysiology involves Rho‐associated kinase (ROCK) signalling activation, we investigated the effect of various ROCK inhibitors on the expression of ECM proteins and proteolytic enzymes using ex vivo and in vitro models.

Methods: Endothelial cell‐Descemet membrane lamellae (DM) from donor corneas (n = 20) and FECD patients (n = 100) undergoing Descemet membrane endothelial keratoplasty were used as ex vivo model. A human corneal endothelial cell line (HCEC‐12) served as in vitro model. Rho‐ROCK signalling pathway components and the effects of the ROCK inhibitors ripasudil (10/30 μM), Y‐27632 (10/30 μM), and netarsudil (1 μM) on the expression of ECM proteins and proteolytic enzymes were analysed, with or without addition of transforming growth factor β1 (TGFβ1, 5 ng/ml), using quantitative real‐time PCR and Western Blot analysis.

Results: Constitutive expression of components of the Rho‐ROCK signalling pathway was higher in DM specimens from FECD patients compared to DM from normal donors. Stimulation with all three ROCK inhibitors significantly downregulated the expression of ECM genes, such as collagen 3 alpha 1 (COL3A1) and fibronectin 1 (FN1), in both FECD and normal DM as well as in HCEC‐12, compared to untreated controls, with ripasudil showing the most significant effect. Downregulation of COL1A1 and FN1 by ripasudil was verified on protein level as well. Ripasudil also suppressed the TGFβ‐induced expression and phosphorylation of downstream molecules of the TGFβ pathway (SMAD2) as well as of the Rho‐ROCK pathway (MLC2). Ripasudil further upregulated gene expression of proteolytic enzymes, e.g. matrix metalloproteinase 1 (MMP1) and MMP3.

Conclusions: These findings suggest that inhibition of ROCK signalling in FECD patients may have a beneficial effect by suppressing expression and stimulating turnover of abnormal ECM components.
In vitro and in vivo characterization of BIO203, a new amide norbixin conjugate with improved pharmacokinetic profile. Potential for oral treatment of age‐related retinal degeneration
Authors: Fontaine Valérie , Camelo Serge , Christine Balducci , Laurence Dinan , Monteiro Elodie , Boumedine Thinhinane , Nguyen Vincent , Fournié Mylene , Clatot Justine , Latil Mathilde , Veillet Stanislas , Lafont René , Dilda Pierre
Published: December 2022

Purpose: We have previously shown that 9′‐cis‐norbixin (norbixin) protects retinal pigmented epithelium (RPE) cells against phototoxicity induced by blue light and N‐retinylidene‐N‐retinylethanolamine (A2E) in vitro and preserves visual function in animal models of dry Age‐related Macular Degeneration (AMD) in vivo. The purpose of this study was to examine the mode of action and the in vitro and in vivo effects of CN30, a norbixin monoamide conjugate.

Methods: Ocular pharmacokinetics in rats administered orally with 50 mg/kg of norbixin, or its conjugate (CN30) were compared. Their effect on photoprotection of primary porcine RPE cells challenged with A2E and blue‐light illumination was quantified. The effects of CN30 on the A2E‐induced transactivation of PPARs, AP‐1 and NF‐κB were measured by reporter gene luciferase activity. The expression of IL‐6, IL‐8, and VEGF was measured by RT‐QPCR. The in vivo neuroprotective effect of intraperitoneally administered CN30 was evaluated by measuring retinal thickness and electroretinogram (ERG) amplitudes in a blue‐light damage (BLD) acute model in albino rats. CN30 efficacy was also assessed by ERG after 6 months oral supplementation in Abca4−/− Rdh8−/− mice.

Results: Compared to norbixin, CN30 displays improved stability and enhanced ocular maximal concentration and exposure (AUC). Similar to our previous observation with norbixin, CN30 mode of action involves the inhibition of PPARs, NF‐κB and AP‐1 transactivation. CN30 reduces IL‐6, IL‐8 and VEGF expression induced by A2E in vitro. In vivo, CN30 protects visual function and retinal structure in albino rats subjected to BLD in an acute model of retinal degeneration. Moreover, 6 months oral supplementation also improve visual function in a model of dry AMD: the Abca4−/− Rdh8−/− double knock‐out mice.

Conclusions: CN30 retains the protective properties of norbixin in vitro and in vivo, and displays improved stability and pharmacokinetic properties. This could open new avenues for the oral treatment of retinal degenerative diseases such as dry AMD.
Self‐reported preference of eyedrops in the treatment of glaucoma – Relation, symptoms, and quality of life
Authors: Saruhanian Arevak , Andreasen Jens Rovelt , Petersen Anne Toft , Korsgaard Maiken , Kolko Miriam
Published: December 2022

Purpose: The purpose of this questionnaire was to investigate how glaucoma patients relate to preservatives in eyedrops and the impact on their quality of life and eye discomfort.

Methods: This study was designed as a questionnaire‐based cross‐sectional study. Inclusion criteria included the use of IOP‐lowering eyedrops, age ≥ 18, and the ability to read and understand Danish. Questionnaires with inadequate replies or self‐rated compliance ≤60% were excluded. Participants were classified into two groups: participants using only preservative‐free eyedrops (PF) and participants using preservative‐containing (PC) – including individuals using a combination of both types of eyedrops. A total of 146 questionnaires were included. These were further divided into 3 groups depending on complete data: questionnaires with complete data in the Glaucoma Symptom Scale (GSS) (133/146), the Glaucoma Quality of Life‐15 (GQL‐15) (135/146), and eye discomfort data (140/146).

Results: No statistically significant differences were found between the groups concerning the total GSS score (PC: 66.16 ± 21.49 vs. PF: 67.55 ± 21.77; p > 0.05), the total GQL‐15 score (PC 30.31 ± 15.13 vs. 31.33 ± 16.80; p > 0.05), or the total eye discomfort score (PC/PF OR; 0.90, 95% CI; 0.66–1.21, p > 0.05). Moreover, we found that the majority of the participants in the PC group were unaware of the preservative status of their eyedrops (PC; 74%), as well as the possibility to avoid preservatives (PC; 67%), by using a preservative‐free alternative. Similarly, most participants of both groups were willing to pay more for preservative‐free eyedrops (PC; 83%, PF; 93%).

Conclusions: No significant difference in GSS, GQL‐15 or eye discomfort was observed between persons treated with PC and PF. A severe lack of information was however observed regarding patient awareness of the preservative status of IOP‐lowering eyedrops, as well as a willingness to pay more to avoid preservatives.
Scanning laser ophthalmoscopy – basic optical principles
Authors: Irsch Kristina
Published: December 2022

Scanning Laser Ophthalmoscopy (SLO) produces an ocular fundus image by moving a focused laser beam via scanning mirrors over the retina in a grid pattern and registering the reflected light from each scanned point. In confocal SLO, a pinhole is placed in front of the detector to cut off scattered or defocused light coming from outside the point of interest, which otherwise can blur the image. This results in a focused, high‐contrast image of a single tissue layer located at the focal plane. Tomographic information can be extracted by moving the plane of the pinhole. The use of various wavelengths allows for different applications, such as fluorescein angiography, indocyanine green angiography, and autofluorescence imaging. This lecture will present the basic principles of SLO, as well as discuss notable applications and variants of the technology.
Optical coherence tomography – Machine learning
Authors: Bernardes Rui
Published: December 2022

Machine learning is a method of data analysis. It gives computers the ability to learn from data and build models from which predictions can be made. Even though OCT (Optical Coherence Tomography) is mainly used to visualize retinal structures and compute thickness maps, it conveys information on subtle changes within the retina before structural ones can be identified. Exposing the machine learning model to a set of examples allows it to build a model from which predictions can be made on new data and explain differences between groups. This lecture will explain the underlying principles of machine learning and discuss potential applications in ophthalmology and CNS disorders through the imaging of the retina.