Concurrent validation of the resistance intensity scale for exercise for monitoring velocity-based training with elastic bands.

The aim was to evaluate the concurrent validity and reliability of the Resistance Intensity Scale for Exercise [RISE], which uses verbal descriptors, to quantify the intensity in velocity-based training with elastic bands. Eighteen trained volunteers performed parallel squats at maximum speed at 40%, 55%, 70%, and 85%1RM in four sessions, two for familiarization and two for reliability. Each set was stopped at a 10% intra-set velocity loss. Participants reported the perceived effort (easy-low-moderate-hard-maximal) at the first and last repetition. The concurrent validation was conducted with external load (i.e., mean propulsive velocity, weight, repetitions, and maximum power) and internal load parameters (i.e., heart rate). Participants' relative strength was calculated to assess its influence on the dependent variable. Acceptable concurrent validity and reliability (ICC>0.77, CV<21%) were observed, with the perceived effort being appropriate to differentiate between intensities and not being influenced by the participants' relative strength (p = 0.88). A categorical linear regression showed significant (p < 0.001) associations between the RISE scores and the weight, repetitions, and mean propulsive velocity (r = 0.43-0.63). The findings certify the usefulness of the perceived exertion for quantifying the intensity during velocity-based training with elastic bands. The perceived exertion of the first and last repetition favors a proper dosage of the training load.

Transcriptional patterns of human retinal pigment epithelial cells under protracted high glucose.

BACKGROUND: The retinal pigment epithelium (RPE) is essential for retinal homeostasis. Comprehensively exploring the transcriptional patterns of diabetic human RPE promotes the understanding of diabetic retinopathy (DR). METHODS AND RESULTS: A total of 4125 differentially expressed genes (DEGs) were screened out from the human primary RPE cells subjected to prolonged high glucose (HG). The subsequent bioinformatics analysis is divided into 3 steps. In Step 1, 21 genes were revealed by intersecting the enriched genes from the KEGG, WIKI, and Reactome databases. In Step 2, WGCNA was applied and intersected with the DEGs. Further intersection based on the enrichments with the GO biological processes, GO cellular components, and GO molecular functions databases screened out 12 candidate genes. In Step 3, 13 genes were found to be simultaneously up-regulated in the DEGs and a GEO dataset involving human diabetic retinal tissues. VEGFA and ERN1 were the 2 starred genes finally screened out by overlapping the 3 Steps. CONCLUSION: In this study, multiple genes were identified as crucial in the pathological process of RPE under protracted HG, providing potential candidates for future researches on DR. The current study highlights the importance of RPE in DR pathogenesis.

Effect of adalimumab as an anti-inflammatory agent on gene expression of retinal pigment epithelial cells.

Adalimumab (ADA) is an anti-inflammatory antibody that has FDA approval as a systemic medication for treating noninfectious uveitis. It is also provisionally being investigated as an intravitreal injection for various retinal conditions. This study aimed to assess the effect of ADA on apoptotic, inflammatory, and fibrogenesis gene expression at mRNA and protein levels in retinal pigment epithelial (RPE) cells. RPEs were treated with serial concentrations of ADA (0.5x, x, 2x, and 4x; [x = 250 µg/mL]) for 24 hours. MTT assay was done and the mRNA and protein expressions were quantified using real-time PCR and ELISA assay, respectively. The mRNA levels of IL-1b and IL-6 were significantly increased in ADA-treated RPEs at 0.5x and x concentrations. However, the increase in cytokine secretion was observed only in IL-1b at x concentration. TGF-ß was significantly upregulated in the 0.5x and 4x doses of ADA both at mRNA and protein levels. MTT assay, along with an unchanged BCL-2/BAX ratio confirmed the safety of ADA on RPEs at all studied concentrations. In conclusion, despite its safety, the 2x concentration of ADA was the only dose that did not ignite the expression of any of the studied inflammatory and fibrogenesis genes. This dosage, which is roughly equal to 2 mg intravitreal dose in a clinical setting, might be referred to as a reference starting point for future in-vivo studies in ocular conditions.

Roles of transmembrane protein 135 in mitochondrial and peroxisomal functions - implications for age-related retinal disease.

Aging is the most significant risk factor for age-related diseases in general, which is true for age-related diseases in the eye including age-related macular degeneration (AMD). Therefore, in order to identify potential therapeutic targets for these diseases, it is crucial to understand the normal aging process and how its mis-regulation could cause age-related diseases at the molecular level. Recently, abnormal lipid metabolism has emerged as one major aspect of age-related symptoms in the retina. Animal models provide excellent means to identify and study factors that regulate lipid metabolism in relation to age-related symptoms. Central to this review is the role of transmembrane protein 135 (TMEM135) in the retina. TMEM135 was identified through the characterization of a mutant mouse strain exhibiting accelerated retinal aging and positional cloning of the responsible mutation within the gene, indicating the crucial role of TMEM135 in regulating the normal aging process in the retina. Over the past decade, the molecular functions of TMEM135 have been explored in various models and tissues, providing insights into the regulation of metabolism, particularly lipid metabolism, through its action in multiple organelles. Studies indicated that TMEM135 is a significant regulator of peroxisomes, mitochondria, and their interaction. Here, we provide an overview of the molecular functions of TMEM135 which is crucial for regulating mitochondria, peroxisomes, and lipids. The review also discusses the age-dependent phenotypes in mice with TMEM135 perturbations, emphasizing the importance of a balanced TMEM135 function for the health of the retina and other tissues including the heart, liver, and adipose tissue. Finally, we explore the potential roles of TMEM135 in human age-related retinal diseases, connecting its functions to the pathobiology of AMD.

Intraocular mRNA delivery with endogenous MmPEG10-based virus-like particles.

Virus-like particles (VLP) are a promising tool for intracellular gene delivery, yet their potential in ocular gene therapy remains underexplored. In this study, we bridged this knowledge gap by demonstrating the successful generation and application of vesicular stomatitis virus glycoprotein (VSVG)-pseudotyped mouse PEG10 (MmPEG10)-VLP for intraocular mRNA delivery. Our findings revealed that PEG10-VLP can efficiently deliver GFP mRNA to adult retinal pigment epithelial cell line-19 (ARPE-19) cells, leading to transient expression. Moreover, we showed that MmPEG10-VLP can transfer SMAD7 to inhibit epithelial-mesenchymal transition (EMT) in RPE cells effectively. In vivo experiments further substantiated the potential of these vectors, as subretinal delivery into adult mice resulted in efficient transduction of retinal pigment epithelial (RPE) cells and GFP reporter gene expression without significant immune response. However, intravitreal injection did not yield efficient ocular expression. We also evaluated the transduction characteristics of MmPEG10-VLP following inter-cameral delivery, revealing transient GFP protein expression in corneal endothelial cells without significant immunotoxicities. In summary, our study established that VSVG pseudotyped MmPEG10-based VLP can transduce mitotically inactive RPE cells and corneal endothelial cells in vivo without triggering an inflammatory response, underscoring their potential utility in ocular gene therapy.

The Exercise Intensity-Music-Tempo Preference Relationship: A Decennial Revisit.

Tempo is a key determinant of the motivational effects of music during exercise and has been the focus of numerous empirical studies (e.g., Karageorghis & Jones, 2014). The present study sought to address the limitations of previous related work and revisit the relationship between exercise intensity and music-tempo preference using unfamiliar, non-lyrical music (to isolate the tempo manipulation). A within-within experimental design was employed to test hypotheses pertaining to the non-linear relationship and associated psychological outcomes (e.g., core affect and state attention). Twenty-four participants (Mage = 20.6 years, SD = .92 years) exercised at five intensities (10% of peak VO2 below ventilatory threshold [VT]; 5% of peak VO2 below VT, at VT, midway between VT and the respiratory compensation point [RCP], and at RCP) during which they were administered music tracks at four tempi (90 bpm, 110 bpm, 130 bpm and 150 bpm) and a no-music control. A music liking item, measures of core affect (valence and arousal), attentional focus and perceived exertion were recorded during the exercise bouts. Results indicated that unlike previous findings with familiar, lyrical music, there was no discernible relationship between exercise intensity and preference for music tempo. The most positive psychological outcomes were associated with fast-tempo music. In accord with previous findings, slow-tempo music attracted low liking scores and the least desirable psychological outcomes at every exercise intensity. The present findings have implications for the use of unfamiliar, non-lyrical music during exercise. Specifically, that such music should be ∼10 bpm faster than familiar, lyrical music.

Effects of Blood flow Restriction and Load on Mean Propulsive Velocity and Subjective Perceived Exertion During Squat and Bench Press Exercises.

BACKGROUND: The aim of this study was to determine the influence of different percentages of blood flow restriction (BFR) and loads on mean propulsive velocity (MPV) and subjective perceived exertion during squat (SQ) and bench press (BP) exercises. HYPOTHESIS: Higher percentages of BFR will positively affect dependent variables, increasing MPV and reducing perceived exertion. STUDY DESIGN: Cross-sectional study. LEVEL OF EVIDENCE: Level 3. METHODS: Eight healthy young male athletes took part. Two sets of 6 repetitions at 70% 1-repetition maximum (1RM), 2 sets of 4 repetitions at 80% 1RM, and 2 sets of 2 repetitions at 90% 1RM were performed randomly; 5-minute recoveries were applied in all sets. The varying arterial occlusion pressure (AOP) applied randomly was 0% (Control [CON]), 80%, and 100%. RESULTS: No statistically significant differences in MPV were found during the BP exercise at any percentage of BFR at any percentage 1RM. During the SQ exercise, MPV results showed statistically significant increases of 5.46% (P = 0.04; ηp2 = 0.31) between CON and 100% AOP at 90% 1RM. The perceived exertion results for the BP exercise showed statistically significant reductions of -8.66% (P < 0.01; ηp2 = 0.06) between CON and 100% AOP at 90% 1RM. During the SQ exercise, the perceived exertion results showed significant reductions of -10.04% (P = 0.04; ηp2 = 0.40) between CON and 100% AOP at 80% 1RM; -5.47% (P = 0.02; ηp2 = 0.48) between CON and 80% AOP at 90% 1RM; and -11.83% (P < 0.01; ηp2 = 0.66) between CON and 100% AOP at 90% 1RM. CONCLUSION: BFR percentages ~100% AOP at 90% 1RM improved acutely MPV (only in SQ exercises) and reduced acutely perceived exertion (in both exercises). These findings are important to consider when prescribing resistance training for healthy male athletes.

RAR Inhibitors Display Photo-Protective and Anti-Inflammatory Effects in A2E Stimulated RPE Cells In Vitro through Non-Specific Modulation of PPAR or RXR Transactivation.

N-retinylidene-N-retinylethanolamine (A2E) has been associated with age-related macular degeneration (AMD) physiopathology by inducing cell death, angiogenesis and inflammation in retinal pigmented epithelial (RPE) cells. It was previously thought that the A2E effects were solely mediated via the retinoic acid receptor (RAR)-α activation. However, this conclusion was based on experiments using the RAR "specific" antagonist RO-41-5253, which was found to also be a ligand and partial agonist of the peroxisome proliferator-activated receptor (PPAR)-γ. Moreover, we previously reported that inhibiting PPAR and retinoid X receptor (RXR) transactivation with norbixin also modulated inflammation and angiogenesis in RPE cells challenged in the presence of A2E. Here, using several RAR inhibitors, we deciphered the respective roles of RAR, PPAR and RXR transactivations in an in vitro model of AMD. We showed that BMS 195614 (a selective RAR-α antagonist) displayed photoprotective properties against toxic blue light exposure in the presence of A2E. BMS 195614 also significantly reduced the AP-1 transactivation and mRNA expression of the inflammatory interleukin (IL)-6 and vascular endothelial growth factor (VEGF) induced by A2E in RPE cells in vitro, suggesting a major role of RAR in these processes. Surprisingly, however, we showed that (1) Norbixin increased the RAR transactivation and (2) AGN 193109 (a high affinity pan-RAR antagonist) and BMS 493 (a pan-RAR inverse agonist), which are photoprotective against toxic blue light exposure in the presence of A2E, also inhibited PPARs transactivation and RXR transactivation, respectively. Therefore, in our in vitro model of AMD, several commercialized RAR inhibitors appear to be non-specific, and we propose that the phototoxicity and expression of IL-6 and VEGF induced by A2E in RPE cells operates through the activation of PPAR or RXR rather than by RAR transactivation.

Anti-inflammatory potential of simvastatin and amfenac in ARPE-19 cells; insights in preventing re-detachment and proliferative vitreoretinopathy after rhegmatogenous retinal detachment surgery.

PURPOSE: Rhegmatogenous retinal detachment is a severe vision-threatening complication that can result into proliferative vitreoretinopathy (PVR) and re-detachment of the retina if recovery from surgery fails. Inflammation and changes in retinal pigment epithelial (RPE) cells are important contributors to the disease. Here, we studied the effects of simvastatin and amfenac on ARPE-19 cells under inflammatory conditions. METHODS: ARPE-19 cells were pre-treated with simvastatin and/or amfenac for 24 h after which interleukin (IL)-1α or IL-1ß was added for another 24 h. After treatments, lactate dehydrogenase release, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) processing, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activity, prostaglandin E2 (PGE2) level, and extracellular levels of IL-6, IL-8, monocytic chemoattractant protein (MCP-1), vascular endothelial growth factor (VEGF), and pigment epithelium-derived factor, as well as the production of reactive oxygen species (ROS) were determined. RESULTS: Pre-treatment of human ARPE-19 cells with simvastatin reduced the production of IL-6, IL-8, and MCP-1 cytokines, PGE2 levels, as well as NF-κB activity upon inflammation, whereas amfenac reduced IL-8 and MCP-1 release but increased ROS production. Together, simvastatin and amfenac reduced the release of IL-6, IL-8, and MCP-1 cytokines as well as NF-κB activity but increased the VEGF release upon inflammation in ARPE-19 cells. CONCLUSION: Our present study supports the anti-inflammatory capacity of simvastatin as pre-treatment against inflammation in human RPE cells, and the addition of amfenac complements the effect. The early modulation of local conditions in the retina can prevent inflammation induced PVR formation and subsequent retinal re-detachment.

Basketball Fatigue Impact on Kinematic Parameters and 3-Point Shooting Accuracy: Insights across Players' Positions and Cardiorespiratory Fitness Associations of High-Level Players.

This study investigated the impact of basketball-induced fatigue on 3-point jump shooting accuracy, the ball's entry angle (EA) into the hoop, shot release time (RT), their relationship with player positions in high-level basketball, and the correlation between cardiorespiratory fitness markers and potential shooting performance changes. Guards (n = 13), forwards (n = 13), and centers (n = 12) underwent physiological assessments. Sequentially, they performed 15 jump shots (PRE), a basketball exercise simulation (BEST) involving 24 × 30 s circuit activities, and a repeated shooting test (POST). The study design was double-blind. The results revealed significant differences (p ≤ 0.05) in RT, EA, and successful shots (SSs) between PRE and POST in each group. The percentage changes from PRE to POST conditions across guards, forwards, and centers were for RT: 25.34% [95%CI: 1.7-48.98], 19.73% [95%CI: -1.9-41.36], 14.95% [95%CI: -5.23-35.13]; for EA: -3.89% [95%CI: -14.82-7.04], -3.13% [95%CI: -12.9-6.64], -3.47% [95%CI: -14.19-7.25]; and for SS: -14.42% [95%CI: -36.5-7.66], -16.76% [95%CI: -40.81-7.29], -19.44% [95%CI: -46.7-7.82], respectively. Post-test differences (p ≤ 0.05) highlighted greater fatigue impact on RT, EA, and SS from guards to centers. Additionally, significant correlations (p ≤ 0.05) were found between the ventilatory threshold, mean HR during BEST, and changes in RT, EA, and SS. This study highlights the substantial impact of basketball-induced fatigue on 3-point shooting parameters across player positions and the interplay with cardiorespiratory factors post-fatigue. Tailored training, considering heart rate, is crucial to optimizing shooting performance.

Screening and evaluation of antioxidants for retinal pigment epithelial cell protection: L-ergothioneine as a novel therapeutic candidate through NRF2 activation.

The continual exposure of retinal tissues to oxidative stress leads to discernible anatomical and physiological alterations. Specifically, the onslaught of oxidative damage escalates the irreversible death of retinal pigmented epithelium (RPE) cells, pinpointed as the fundamental pathological event in dry age-related macular degeneration (AMD). There is a conspicuous lack of effective therapeutic strategies to counteract this degenerative process. This study screened a library of antioxidants for their ability to protect RPE cells against oxidative stress and identified L-ergothioneine (EGT) as a potent cytoprotective agent. L-ergothioneine provided efficient protection against oxidative stress-damaged RPE and maintained cell redox homeostasis and normal physiological functions. It maintained the normal structure of the retina in mice under oxidative stress conditions. Transcriptomic analysis revealed that EGT counteracted major gene expression changes induced by oxidative stress. It upregulated antioxidant gene expression and inhibited NRF2 translocation. The inhibition of NRF2 abolished EGT's protective effects, suggesting that NRF2 activation contributes to its mechanism of action. In conclusion, we identified EGT as a safe and effective small-molecule compound that is expected to be a novel antioxidative agent for treating AMD.

Retinal response to light exposure in BEST1-mutant dogs evaluated with ultra-high resolution OCT.

Mutations in BEST1 cause an autosomal recessive disease in dogs where the earliest changes localize to the photoreceptor-RPE interface and show a retina-wide micro-detachment that is modulated by light exposure. The purpose of this study was to define the spatial and temporal details of the outer retina and its response to light with ultra-high resolution OCT across a range of ages and with different BEST1 mutations. Three retinal regions were selected in each eye: near the fovea-like area, near the optic nerve, both in the tapetal area, and inferior to the optic nerve in the non-tapetal area. The OS+ slab thickness was defined between the peak near the junction of inner and outer segments (IS/OS) and the transition between basal RPE, Bruch membrane, choriocapillaris and proximal tapetum (RPE/T). In wildtype (WT) dogs, two tapetal regions showed additional hyperscattering OCT peaks within the OS+ slab likely representing cone and rod outer segment tips (COST and ROST). The inferior non-tapetal region of WT dogs had only one of these peaks, likely ROST. In dogs with BEST1 mutations, all three locations showed a single peak, likely suggesting optical silence of COST. Light-dependent expansion of the micro-detachment by about 10 um was detectable in both tapetal and non-tapetal retina across all ages and BEST1 mutations.

Heimler syndrome with a complaint of blurred vision caused by compound heterozygous variants in PEX1.

INTRODUCTION: Heimler syndrome (HS) is a rare disorder that includes sensorineural hearing loss (SNHL), nail abnormalities, and enamel hypoplasia. Patients with this syndrome can also exhibit ocular manifestations. At present, only a few cases of HS have been reported, existing knowledge of this syndrome is limited, and many cases have been misdiagnosed or even missed. This is the first report of Heimler syndrome with blurred vision as the first complaint, which was diagnosed by genetic analysis in the ophthalmology department. CASE DESCRIPTION: An 8-year-old girl complained of bilateral visual blur and night blindness from birth. Ophthalmic examinations revealed bilateral retinitis pigmentosa with cystoid macular edema, visual impairment with hyperopia and astigmatism. Hearing test revealed bilateral severe sensorineural hearing loss. Dental examinations revealed enamel hypoplasia. In addition, whole-exome sequencing (WES) identified two pathogenic variants in PEX1: the previously reported missense variant c.2966T > C (p.I989 T), and the novel frameshift variant c.1671_1672del (p.G558Sfs*33). CONCLUSION: Heimler syndrome is caused by compound heterozygous PEX1 pathogenic variants, c.2966T > C (p.I989 T) and c.1671_1672del (p.G558Sfs*33), which contributed to the diversity of clinical and genetic profiles in this patient. The main clinical manifestations include bilateral retinitis pigmentosa with cystoid macular edema, sensorineural hearing loss, and enamel hypoplasia. Systemic examinations are suggested for patients suspected of having pigmentary retinal dystrophy, especially combined with hearing-related impairments. Genetic testing can help us to make a definitive diagnosis.

Spontaneous Massive Retinal Pigment Epithelium Tear: A Case Report of a Dramatic Complication of Age-Related Macular Degeneration.

Retinal pigment epithelium (RPE) tears occur when the RPE acutely breaks and retracts, leaving the underlying Bruch's membrane and choroid exposed. They usually happen in areas of previous pigment epithelial detachments and are generally associated with age-related macular degeneration (AMD). The purpose of this report is to describe a case of a spontaneous massive central RPE tear in a patient with untreated AMD. A 67-year-old female patient presented with complaints of sudden decreased vision in her right eye. Her best-corrected visual acuity was 2/20, and fundoscopy revealed a massive central retinal hemorrhage with intraretinal, subretinal, and sub-RPE blood. The patient started anti-vascular endothelial growth factor (VEGF) treatment, and after the blood was reabsorbed, a very large central tear of the RPE involving the central macula was evident, with a layer of detached retina folded on itself. She received continuous anti-VEGF therapy, and the final measurement of her visual acuity was 2/200, despite the complete reabsorption of the hemorrhage. RPE tears may occur spontaneously as part of the natural history of AMD or be triggered by the initiation of anti-VEGF treatment in the presence of large pigment epithelium detachments. There are currently no strategies to prevent their spontaneous development, and they constitute a dramatic complication of AMD. The prognosis is dependent on the size and location of the lesion, and the visual loss is irreversible.

Pluripotent stem cell-derived models of retinal disease: Elucidating pathogenesis, evaluating novel treatments, and estimating toxicity.

Blindness poses a growing global challenge, with approximately 26% of cases attributed to degenerative retinal diseases. While gene therapy, optogenetic tools, photosensitive switches, and retinal prostheses offer hope for vision restoration, these high-cost therapies will benefit few patients. Understanding retinal diseases is therefore key to advance effective treatments, requiring in vitro models replicating pathology and allowing quantitative assessments for drug discovery. Pluripotent stem cells (PSCs) provide a unique solution given their limitless supply and ability to differentiate into light-responsive retinal tissues encompassing all cell types. This review focuses on the history and current state of photoreceptor and retinal pigment epithelium (RPE) cell generation from PSCs. We explore the applications of this technology in disease modelling, experimental therapy testing, biomarker identification, and toxicity studies. We consider challenges in scalability, standardisation, and reproducibility, and stress the importance of incorporating vasculature and immune cells into retinal organoids. We advocate for high-throughput automation in data acquisition and analyses and underscore the value of advanced micro-physiological systems that fully capture the interactions between the neural retina, RPE, and choriocapillaris.

Recent Achievements in the Heterogeneity of Mammalian and Human Retinal Pigment Epithelium: In Search of a Stem Cell.

Retinal pigment epithelium (RPE) cells are important fundamentally for the development and function of the retina. In this regard, the study of the morphological and molecular properties of RPE cells, as well as their regenerative capabilities, is of particular importance for biomedicine. However, these studies are complicated by the fact that, despite the external morphological similarity of RPE cells, the RPE is a population of heterogeneous cells, the molecular genetic properties of which have begun to be revealed by sequencing methods only in recent years. This review carries out an analysis of the data from morphological and molecular genetic studies of the heterogeneity of RPE cells in mammals and humans, which reveals the individual differences in the subpopulations of RPE cells and the possible specificity of their functions. Particular attention is paid to discussing the properties of "stemness," proliferation, and plasticity in the RPE, which may be useful for uncovering the mechanisms of retinal diseases associated with pathologies of the RPE and finding new ways of treating them.

Use, failure, and non-compliance of respiratory personal protective equipment and risk of upper respiratory tract infections-A longitudinal repeated measurement study during the COVID-19 pandemic among healthcare workers in Denmark.

INTRODUCTION: Upper respiratory tract infections (URTI) are common and a common cause of sick-leave for healthcare workers, and furthermore pose a threat especially for patients susceptible to other diseases. Sufficient use of respiratory protective equipment (RPE) may protect both the workers and the patients. The COVID-19 pandemic provided a unique opportunity to study the association between use of RPE and URTI in a real-life setting. The aim of this study was to examine if failure of RPE or non-compliance with RPE guidelines increases the risk of non-COVID-19 URTI symptoms among healthcare workers. METHODS: In a longitudinal cohort study, we collected self-reported data daily on work tasks, use of RPE, and URTI symptoms among healthcare workers with patient contact in 2 Danish Regions in 2 time periods during the COVID-19 pandemic. The association between failure of RPE or non-compliance with RPE guidelines and URTI symptoms was analyzed separately by generalized linear models. Persons tested positive for severe acute respiratory syndrome coronavirus 2 were censored from the analyses. The 2 waves of data collection were analyzed separately, as there were differences in recommendations of RPE during the 2 waves. RESULTS: We found that for healthcare workers performing work tasks with a risk of transmission of viruses or bacteria, failure of RPE was associated with an increased risk of URTI symptoms, RR: 1.65[0.53-5.14] in wave 1 and RR: 1.30[0.56-3.03] in wave 2. Also non-compliance with RPE guidelines was associated with an increased risk of URTI symptoms compared to the use of RPE in wave 1, RR: 1.28[0.87-1.87] and wave 2, RR: 1.39[1.01-1.91]. Stratifying on high- versus low-risk tasks showed that the risk related to failure and non-compliance was primarily associated with high-risk tasks, although not statistically significant. DISCUSSION: The study was conducted during the COVID-19 pandemic and thus may be affected by other preventive measures in society. However, this gave the opportunity to study the use of RPE in a real-life setting, also in departments that did not previously use RPE. The circumstances in the 2 time periods of data collection differed and were analyzed separately and thus the sample size was limited and affected the precision of the estimates. CONCLUSION: Failures of RPE and non-compliance with RPE guidelines may increase the risk of URTI, compared to those who reported use of RPE as recommended. The implications of these findings are that the use of RPE to prevent URTI could be considered, especially while performing high-risk tasks where other prevention strategies are not achievable.

RPE65 mutations in Leber congenital amaurosis, early-onset severe retinal dystrophy, and retinitis pigmentosa from a tertiary eye care center in India.

INTRODUCTION: Mutations in the retinal pigment epithelial 65 kilodalton protein (RPE65) gene are associated with various inherited retinal diseases (IRDs), including Leber congenital amaurosis (LCA), early-onset severe retinal dystrophy (EOSRD), and retinitis pigmentosa (RP). We screened for mutations in RPE65 in a series of Indian patients with these IRDs to determine the frequency/types of mutations and to describe the associated phenotypes. MATERIALS AND METHODS: Diagnosis of LCA, EOSRD, and RP was made by standard and pre-defined criteria. Patients were evaluated by clinical, retinal imaging, and electrophysiological parameters. Genomic DNA from patients and available family members were used for identifying mutations by direct Sanger sequencing of the RPE65 gene or targeted NGS gene panel for IRDs covering 260+ genes. Variations detected were tested in healthy control populations and for co-segregation with the disease in available family members. RESULTS: Mutations were found in eight patients, out of 220 total cases screened, all homozygous for the respective mutant alleles. Seven patients had mutations leading to premature termination codons and one patient had a missense change. The onset of visual loss ranged from birth to <2 years of life. At presentation, RPE mottling in the background retina was present in all cases with macular involvement in five cases with or without vascular attenuation and optic disc pallor. CONCLUSION: RPE65 mutations in this series were found in 3.6% of cases associated with severe, early-onset disease, with consistent RPE mottling and variable manifestations with regard to the extent of disc pallor, arteriolar attenuation, and appearance of the macula.

Could internal limiting membrane peeling before Voretigen neparvovec-ryzl subretinal injection prevent focal chorioretinal atrophy?

Purpose: To report the effect of internal limiting membrane (ILM) peeling prior to Voretigen Neparvovec-ryzl (VN) subretinal injection on focal chorioretinal atrophy development in patients presenting with RPE65-mediated Leber congenital amaurosis (LCA). Design: Retrospective case series. Methods: Three patients who underwent bilateral subretinal VN injection for RPE65-mediated LCA were followed up for 18-24 months. ILM peeling was performed unilaterally in patients 1 and 2 and bilaterally in patient 3. Chorioretinal atrophy was identified on fundus biomicroscopy, non-mydriatic retinography and/or ultrawide field fundus imaging. Best corrected visual acuity (BCVA), spectral-domain optical coherence tomography (SD-OCT), visual fields, full-field stimulus threshold (FST) and visual functioning questionnaire score (NEI-VFQ-25) were reported. Outcome measures were changes in BCVA, visual fields, FST, NEI-VFQ-25, and chorioretinal atrophy location. Results: Chorioretinal atrophy at the injection site exclusively developed in eyes which did not undergo prior ILM peeling. In patient 3, bilateral pre-operative nummular chorioretinal alterations progressed toward epithelial atrophic patches in the mid and extreme retinal periphery 18 months after VN injection. BCVA and visual fields improved bilaterally. NEI_VFQ 25 remained stable in patient 1 and improved in patient 2 and 3. FST test improved bilaterally in patient 3. Conclusions: ILM peeling prior to VN injection seems to be a smoother and safer technique to administer VN treatment and may prevent secondary focal atrophy development at the injection site. However, another type of more extended chorioretinal atrophy might exist and could be related to LCA evolution or to incompletely understood adverse effect of VN product.

The features of dome-shape Macula and related complications in high myopia on optical coherence tomography.

PURPOSE: This study used optical coherence tomography scanning and 3D reconstruction of the macular region in high myopia to examine more thoroughly and carefully the differences between high myopia-related macular complications with and without dome-shape macula (DSM) and to determine whether the DSM's fine structure has an effect on them. METHODS: Retrospective analysis of the medical records of 345 eyes with high myopia who underwent an optical coherence tomography (OCT) examination. They were divided into the DSM group (69 eyes) and the group without DSM (276 eyes). Macular complications between the two groups were compared. The height of the DSM and the diameter of the dome base were measured. And then the association between DSM type, protrusion height and macular problems were analyzed. RESULTS: Epiretinal membrane (ERM) and extrafoveal schisis occurred more frequently in the DSM group, but the was no statistically significant difference in the frequency of foveal schisis between the two groups. The majority of eyes in the DSM categorization had a horizontal oval-shaped domain. In the DSM group, there was no evident difference in the percentage of eyes with macular complications in the groups below 150 um and above 150 um. CONCLUSIONS: OCT examination-based fine macular structure analysis reveals that DSM affects various macular problems in distinct ways. DSM could increase the risk of extrafoveal schisis and ERM while decreasing the risk of foveal schisis. The height of the DSM had no obvious impact on the prevalence of macular complications.