Heart Failure Post-SARS-CoV-2 Infection in Children with Duchenne Muscular Dystrophy: The Additive Value of Cardiovascular Magnetic Resonance.

In this case series, we describe the diagnosis of post-COVID-19 myocarditis in asymptomatic patients with Duchenne Muscular Dystrophy (DMD) and a mild COVID-19 disease course. These patients were referred for CMR due to electrocardiographic and echocardiographic alterations, which did not exist before COVID-19 infection. CMR identified the presence of severe myocardial inflammation in all patients based on abnormally elevated myocardial T2 ratio, late gadolinium enhancement, native T1 mapping, T2 mapping, and extracellular volume fraction. This was paired with concurrent impairment of left ventricular function. Appropriate treatment was initiated in all cases. Two of the four patients developed episodes of ventricular tachycardia during the following 6 months, and a defibrillator was implanted. Despite the mild clinical presentation, this case series demonstrates the diagnostic strength of CMR in the diagnosis and evaluation of post-COVID-19 myocarditis and serves to increase awareness of this potential complication amongst treating physicians.

Evaluation of Cardiac, Autonomic Functions in Ambulant Patients with Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder caused by dystrophin gene mutation resulting in muscle weakness, motor delays, difficulty in standing, and inability to walk by 12 years. As disease progresses, it leads to cardiac and respiratory failure. Evaluation of cardiac autonomic status and echocardiography in DMD patients at a young age can be a potential biomarker to assess disease progression. This study aimed to investigate the younger DMD population of 5-11years of age with mild to moderate cardiac involvement for early detection using non-invasive and cost-effective tools. Genetically confirmed male DMD patients, aged 5-11 years (n = 47), screened from the outpatient department of a tertiary neuroscience institution were subjected to heart rate variability and echocardiographic analysis, and values were correlated with their clinical variables. DMD patients showed a significantly higher difference in HR, interventricular septum, E m/s, and E-wave to A-wave (E/A) ratio than normal values (p < 0.001). Significantly higher HR indicates initial sinus tachycardia and decreased IVD (d), and increased E m/s and E/A ratio mark the onset of cardiac symptoms in DMD patients even though its chamber dimension remains normal and are associated with cardiac muscle fibrosis.

Safety and tolerability of losmapimod for the treatment of FSHD

Evaluate the safety and tolerability of losmapimod in the treatment for FSHD. FSHD is a relentless, variably progressive disease leading to accumulation of disability over decades. Fulcrum is developing losmapimod, a small molecule p38 alpha/beta MAPK inhibitor, to treat FSHD. Losmapimod has been generally well-tolerated in more than 3,600 subjects across multiple clinical studies, including >100 subjects with FSHD. Fulcrum has assessed losmapimod in FSHD in one completed phase 1 study (FIS 001-2018) and two ongoing Phase 2 studies in the open label extension period (FIS 001-2019 and FIS 002-2019). Subjects aged 18-65 years with genetically confirmed FSHD1, clinical severity score 2-4, and MRI-eligible muscles for biopsy were exposed to losmapimod 7.5 or 15 mg twice daily PO for 14 days and up to 76 weeks. In study FIS 001-2018, 6 subjects were exposed to 7.5 mg and 11 subjects to 15 mg twice daily dosing for 14 consecutive days. In studies FIS 001-2019 and FIS 002-2019, 14 and 77 subjects respectively, received at least one dose of losmapimod 15 mg twice daily for up to 76 weeks. A total of 108 subjects with FSHD1 have been exposed to losmapimod, with approximately 131 patient-years of exposure. Fifty-seven subjects have been exposed to losmapimod for 12 to 18 months, and 30 have been exposed for over 18 months. Most adverse events (AEs) observed during the studies were considered of mild to moderate in severity. The most common AEs were alanine aminotransferase (ALT) increase, headache, dizziness, dry skin, eczema and gastrointestinal disorders. The majority of AEs resolved with continued dosing. Dosing has been paused for 14 days in four subjects (3 in FIS 001-2019 and 1 in FIS 002-2019) subjects due to COVID-19 infection. There were no reported drug related SAEs, deaths, discontinuations due to AEs, or clinically significant changes in vital signs, clinical laboratory results, or ECG parameters. Losmapimod given as up to 15 mg twice daily in >100 subjects with FSHD1 for up to 76 weeks has been generally well-tolerated, consistent with that previously reported in other patient populations. Therefore, the benefit-risk profile of losmapimod for the treatment of FSHD remains favorable.Copyright © 2022

42nd Scientific Meeting of the German Society for Magnesium Research

The proceedings contain 23 papers. The topics discussed include: Mg and skeletal system: a link to osteoporosis and osteoarthritis;a putative impact of IL-6 on the expression of magnesiotropic genes through the activation of the JAK/STAT3 pathway;magnesium in pain therapy - historical notes and current aspects;Alzheimer's-associated variant rs708727 might be connected to dementia in Parkinson's disease;effect of magnesium citrate supplementation on the brain tissue of patients with Miyoshi dysferlinopathy measured by 31P magnetic resonance spectroscopy;clinical status of magnesium implants;Ionized magnesium: update 2022;magnesium in the treatment of selected types of muscular dystrophy;magnesium speciation analysis in blood serum;epigenetically-induced modulation of the HPA axis might improve resilience to chronic stress;magnesium status in patients with fibromyalgia syndrome;and post-covid-syndrome and transient microvascular pathology in pulse-wave-analysis - association with Mg/Ca ratio and magnesium therapy-options.

Myotonic dystrophy type 1 in the COVID-19 era.

INTRODUCTION: Myotonic dystrophy type 1 (DM1) is the most prevalent muscular dystrophy in adults. People with DM1 might represent a high-risk population for respiratory infections, including COVID-19. Our aim was to evaluate the characteristics of COVID-19 infection and vaccination rate in DM1 patients. METHODS: This cross-sectional cohort study included 89 patients from the Serbian registry for myotonic dystrophies. Mean age at testing was 48.4 ± 10.4 years with 41 (46.1%) male patients. Mean duration of the disease was 24.0 ± 10.3 years. RESULTS: COVID-19 infection was reported by 36 (40.4%) DM1 patients. Around 14% of patients had a more severe form of COVID-19 requiring hospitalization. The severity of COVID-19 was in accordance with the duration of DM1. A severe form of COVID-19 was reported in 20.8% of patients who were not vaccinated against SARS-CoV-2 and in none of the vaccinated ones. The majority of 89 tested patients (66.3%) were vaccinated against SARS-CoV-2. About half of them (54.2%) received three doses and 35.6% two doses of vaccine. Mild adverse events after vaccination were recorded in 20.3% of patients. CONCLUSIONS: The percentage of DM1 patients who suffered from COVID-19 was like in general population, but with more severe forms in DM1, especially in patients with longer DM1 duration. The study indicated an overall favorable safety profile of COVID-19 vaccines among individuals with DM1 and its ability to protect them from severe COVID-19.

Early immunological responses to the mRNA SARS-CoV-2 vaccine in patients with neuromuscular disorders.

Backgrounds: Intramuscular injection of the SARS-CoV-2 vaccine has raised concerns about its use in patients with neuromuscular disorders (NMDs). We evaluated the response of patients with NMDs to the BNT162b2 vaccine. Methods: Healthy subjects, patients with spinal muscular atrophy (SMA), and patients with Duchenne muscular dystrophy (DMD) were included. All participants received two BNT162b2 doses. SARS-CoV-2 antibody titers at baseline and 2 weeks after each vaccination were compared between groups. Residual muscle volume was evaluated in NMDs group. A questionnaire documented adverse reactions. Results: Eleven patients with NMDs (9 with SMA, 2 with DMD; 7 males; aged 32.7 ± 19.3 years) and 346 healthy subjects (60 males, aged 40.0 ± 12.4 years) were included. Antibody titers (U/mL) were similar between groups (baseline: <0.40 vs. <0.40, first vaccination, 145 ± 258 vs. 103 ± 1192, and second vaccination, 1528 ± 1265 vs. 1429 ± 944; p = 1.000, 0.909, and 0.736, respectively). A negative correlation was found between antibody titers and residual muscle volume but was not significant (Mercuri scale, r = -0.429, p = 0.249; fat infiltration rate, r = -0.194, p = 0.618). The adverse reactions were comparable between groups. Conclusion: The BNT162b2 vaccine is safe and effective in patients with NMDs.

Why Does It Feel Different? Provider Moral Distress in Removing Unwanted Aggressive Intervention for Conscious Patients (TH123B)

Outcomes: 1. Illustrate increased moral distress associated with removing unwanted aggressive interventions for conscious patients compared to unconscious patients. 2. Demonstrate the importance of the interdisciplinary team in supporting providers experiencing moral distress. When providing end-of-life care, removing unwanted aggressive intervention is more challenging in a conscious patient. If the intent to provide comfort and reduce suffering is the same, why does it feel different when the patient is conscious? This case examines the moral distress experienced by the palliative care team who assisted a conscious patient with Duchenne muscular dystrophy achieve his goal of liberation from the ventilator. A 41-year-old male with Duchenne muscular dystrophy and prior COVID-19 infection presented with respiratory failure. The patient had COVID-19 infection in April 2022 and was ventilator dependent since then. The palliative care team was consulted for goals of care discussion. After extensive discussion with the patient and his family, the patient decided to be disconnected from the ventilator and wanted a peaceful passing because long-term ventilatory support was no longer acceptable to him. He was afraid of being aware of struggling to breathe and requested to be asleep throughout this process. Specifically, he said he wanted "to close my eyes and see [my family] on the other side." When the patient was comfortable and asleep as he and his family desired, he was disconnected from the ventilator and died peacefully with his family around him. During this process, the palliative care team's intent was clear: follow the patient's wishes and provide comfort. Ethically, there is no difference in removing unwanted aggressive interventions between conscious and unconscious patients, but the team experienced significantly more distress in this case. After the patient's death, the interdisciplinary team provided support to help the palliative care team work through the distress experienced.Copyright © 2023

Severe Prps1 Deficiency and Response to S-Adenosylmethionine and Nicotinamide Riboside Supplementation

Background: PRPS1 deficiency spectrum is an X-linked condition caused by pathogenic variants in PRPS1, which encodes for the PRPP enzyme involved in the purine synthesis pathway, among other metabolic pathways. Severely affected individuals, also known as Arts syndrome, have congenital sensorineural hearing loss, optic atrophy, developmental delays, ataxia, hypotonia, and recurrent infections. Infections often precipitate worsening of symptoms and many individuals pass away in childhood. Mildly to moderately affected individuals can have isolated hearing loss, also known as DFNX1, or hearing loss with later onset ataxia and optic neuropathy concerns, also known as CMTX5. Given the importance of PRPP in the role of purine synthesis as well as other cellular processes, including formation of NAD(P), supplementation of these pathways is a logical approach for these patients. 2 Arts syndrome patients were previously supplemented with S-adenosylmethionine, starting in mid-childhood, with improvement in infection severity and frequency, as well as stabilization of other symptoms. Recently another Arts syndrome patient was supplemented with S-adenosylmethionine and nicotinamide riboside, starting in early childhood, with improvement in infection frequency and developmental gains. Here we present a now 23 month old male patient with severe PRPS1 deficiency spectrum symptoms, who was started on S-adenosylmethionine and nicotinamide riboside supplementation. Result(s): This is a 23 month old male with developmental delay, retinal dystrophy, congenital bilateral sensorineural hearing loss, and hypotonia with a PRPS1 c.383A > T / p.Asp128Val likely pathogenic variant. He does not have a history of recurrent infections, however family reports relative isolation due to the Covid-19 pandemic. He sat unsupported at 10 months, crawled at 14 months, pulled to stand at 18 months, and is nonverbal. His uric acid testing was in the low range of normal. He had normal purine testing with low normal xanthine and hypoxanthine levels. At 19 months the patient started 20 mg/kg/d S-adenosylmethionine supplementation. At 20 months this was increased to 40 mg/kg/d S-adenosylmethionine and he started on 30 mg/kg/d nicotinamide riboside supplementation. Parents reported subjective improvement in strength and endurance with supplementation. He made significant developmental gains including walking with a walker. He had done well with occasional upper respiratory infections without regression in skills, worsening hypotonia, or increased respiratory needs. Unfortunately, very recently he had a cardiac arrest secondary to respiratory failure from rhinovirus/enterovirus and H. influzenzae pneumonia, for which he remains hospitalized at this time. Conclusion(s): This is the 4th reported patient with severe PRPS1 deficiency treated with S-adenosylmethionine supplementation and the 2nd reported patient treated with nicotinamide riboside supplementation. Both supplements have a limited side effect profile and have a biochemical basis for consideration in PRPS1 deficiency. He initially did well on supplementation with improvements in strength and endurance, as well as developmental gains, however his current trajectory remains to be seen. Unfortunately, NAD/NADP, ADP/ATP, and similar markers were unavailable to us and we plan to continue clinical monitoring on supplementation. Further studies are needed to evaluate the effectiveness of S-adenosylmethionine and nicotinamide riboside supplementation in these patients.Copyright © 2023

Physiotherapy results of a patient with critical illness polyneuropathy due to COVID-19: A case report

The aim of this study is to examine the results of physiotherapy in a patient with critical illness polyneuropathy (CIP) due to coronavirus disease 2019 (CO-VID-19). The 48-year-old male patient with CIP due to COVID-19 was enrolled in a physiotherapy program for 3 months with 5 sessions/week. Pain intensity, motor skills, daily living activities, fatigue level, cognitive status, and decubitus ulcer were evaluated with a visual analogue scale, the Medical Research Coun-cil-Sum Score, the Functional Independence Scale, the Fatigue Severity Scale, the Standardized Mini-Mental Test, and pressure wound staging, respectively. Positive improvements were achieved in functional level, fatigue, pain, and pressure sores with the physiotherapy program for this patient with CIP due to COVID-19. This report provides an idea about the effects of physiotherapy programs for COVID-19-related CIP to academics and clinicians working in this field.Copyright © 2022, Derman Medical Publishing. All rights reserved.

COVID-19 and myotonic dystrophy: Case reports and systematic review.

INTRODUCTION: Steinert's disease is a rare genetic disorder characterized by progressive myotonia and multi-organ damage. It is associated with respiratory and cardiological complications often leading patients to exitus. These conditions are also traditional risk factors for severe COVID-19. SARS-CoV-2 has affected people with chronic diseases, but the impact on people with Steinert's disease is poorly defined, with only a few reported and described. More data are needed to understand whether this genetic disease is a risk factor for more serious evolution or death in patients with COVID-19. METHODOLOGY: The study describes two cases of patients with SD and COVID-19 and summarizes available evidence of the clinical outcome of COVID-19 in patients with Steinert's disease, by performing a systematic review of the literature (following PRISMA statements and performing PROSPERO registration). RESULTS: Overall, 5 cases were retrieved from the literature review, with a median age of 47 years, of whom 4 had advanced SD and unfortunately died. By contrast, the 2 patients from our clinical practice and 1 from literature had a good clinical outcomes. Mortality ranged from 57% (all cases) to 80% (only literature review). CONCLUSIONS: There is a high mortality rate in patients with both Steinert's disease and COVID-19. It highlights the importance of strengthening prevention strategies, especially vaccination. All SD with SARS-CoV-2 infection/COVID-19 patients should be identified early and treated to avoid complications. It is still unknown which treatment regimen is best to use in those patients. Studies on a greater number of patients are necessary to provide clinicians with further evidence.

Neuromuscular disease: 2023 update.

This review highlights ten important advances in the neuromuscular disease field that were reported in 2022. As with prior updates in this article series, the overarching topics include (i) advances in understanding of fundamental neuromuscular biology; (ii) new / emerging diseases; (iii) advances in understanding of disease etiology and pathogenesis; (iv) diagnostic advances; and (v) therapeutic advances. Within this general framework, the individual disease entities that are discussed in more detail include neuromuscular complications of COVID-19 (another look at the topic first covered in the 2021 and 2022 reviews), DNAJB4-associated myopathy, NMNAT2-deficient hereditary axonal neuropathy, Guillain-Barré syndrome, sporadic inclusion body myositis, and amyotrophic lateral sclerosis. In addition, the review highlights a few other advances (including new insights into mechanisms of fiber maturation during muscle regeneration and fiber rebuilding following reinnervation, improved genetic testing methods for facioscapulohumeral and myotonic muscular dystrophies, and the use of SARM1 inhibitors to block Wallerian degeneration) that will be of significant interest for clinicians and researchers who specialize in neuromuscular disease.

Infections by varicella zoster virus in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)

Rationale: APECED is a life-threatening monogenic disorder characterized by multiorgan autoimmunity. Most patients harbor autoantibodies (auto-abs) to type-1 interferons (IFNs), which are important mediators of viral defense. Auto-abs to type-1 IFNs are associated with severe COVID-19 and may play a role in other viral infections including by varicella zoster virus (VZV). A recent study of 44 European APECED patients reported increased susceptibility to VZV, and a correlation between VZV recurrence and auto-abs to IFN-α. The clinical, immunophenotypic, and auto-ab characteristics of APECED patients in the USA with VZV are described. Methods: Data was obtained from 103 participants on a prospective, natural history study after informed consent. Auto-abs to IFN-α, IFN-β or IFN-ω were measured using a multiplex particle-based assay. Unpaired t tests or U Mann Whitney tests were used, with Holm correction for multiple comparisons, where appropriate. Results: Twenty-six patients reported childhood chickenpox (mean onset 5.6 years) and 2 (7.7%) required hospitalization for severe disease. Nineteen patients (18%) had at least one episode of shingles (median onset 13 years;range, 4-55 years) and 4 had >1 episode. Fifteen of the 19 patients with shingles (79%) were not receiving immunosuppressive medications during their first infection. VZV IgG levels;total and percent CD3, CD8, CD4, CD19, NK cells;and auto-abs to IFN-α, IFN-β and IFN-ω did not significantly differ between patients with or without recurrent shingles. Conclusions: A subset of APECED patients develop early-onset, recurrent VZV infections even in the absence of immunosuppression. The mechanisms underlying susceptibility to VZV in APECED require further study.

Safety and immunogenicity of mRNA COVID-19 vaccine in inpatients with muscular dystrophy.

INTRODUCTION/AIMS: Due to muscular weakness and cardiopulmonary dysfunction, patients with muscular dystrophy (MD) have an increased risk of serious complications from coronavirus disease-2019 (COVID-19). Although vaccination is recommended, COVID-19 vaccination safety and immunogenicity in these patients are unknown. We investigated reaction frequency, post-vaccine antibody titers after two mRNA COVID-19 vaccine doses, and clinical predictors of antibody response among patients with MD. METHODS: We recruited 171 inpatients with MD receiving two BNT162b2 mRNA COVID-19 vaccine doses from seven hospitals. Blood samples were obtained from 53 inpatients before the first dose and 28 to 30 days after the second dose, and antibody titers were measured. RESULTS: Overall, 104 (60.8%) and 115 (67.6%) patients had side effects after the first and second doses, respectively. These were generally mild and self-limited. Multiple logistic regression analysis showed that a bedridden state was associated with reduced side effects (odds ratio [OR] = 0.29; 95% confidence interval [CI], 0.12 to 0.71). The antibody titers of all participants changed from negative to positive after two vaccine doses. The geometric mean titer (GMT) of the inpatients was 239 (95% CI, 159.3 to 358.7). Older age (relative risk [RR] = 0.97; 95% CI, 0.95 to 0.99) and bedridden state (RR = 0.27; 95% CI, 0.14 to 0.51) were associated with a lower antibody titer. Patients with myotonic dystrophy type 1 (DM1) had a lower GMT than patients with other MDs (RR = 0.42; 95% CI, 0.21 to 0.85). DISCUSSION: COVID-19 vaccination is safe and immunogenic in inpatients with MD. Patients with DM1 appear to have a poorer COVID-19 antibody response than those with other MDs.

'It becomes the new everyday life' - experiences of chronic pain in everyday life of people with limb-girdle muscular dystrophy.

PURPOSE: To investigate experiences and reflections on challenges in everyday life of people living with limb-girdle muscular dystrophy (LGMD) and chronic pain in order to improve rehabilitation services. MATERIALS AND METHODS: The design for this study was qualitative using the Interpretive Description methodology and the salutogenic theory of Sense of Coherence as the theoretical framework. Four semi-structured focus group interviews were conducted with 19 adults with LGMD from April to May 2021. The interviews were conducted online due to COVID-19. RESULTS: Living with chronic pain and LGMD affected everyday life in terms of the participants' overall Sense of Coherence. Beneficial or unfavorable coping strategies were identified within four interrelated categorical themes: pain management, normality comprehension, affected emotional sentiment and altered identity. CONCLUSION: Healthcare professionals should acknowledge possible chronic pain secondary to LGMD. Chronic pain appears to be a prevalent problem in people with LGMD with negative impact on everyday life, yet patients with LGMD did not receive sufficient information and necessary tools from health professionals to cope with chronic pain. Thus, adequate pain management appeared to be a difficult and self-taught process. Educating health professionals on how to support patients with LGMD and chronic pain is needed.IMPLICATIONS FOR REHABILITATIONHealth professionals should acknowledge and address the possibility of chronic pain secondary to limb-girdle muscular dystrophy (LGMD) and educate patients in pain management.Physiotherapy, energy management and engagement in meaningful activities may help patients gain some control of pain and limit the consequences of pain on everyday life.Supporting patients to accept pain and to shift focus towards their current capabilities may potentially improve pain management.Educating health professionals on how to support patients with LGMD and chronic pain is needed.

The Refinement of Home Exercise Program for Children and Adolescents With Muscular Dystrophy in the Present COVID-19 Pandemic Scenario: A Scoping Review.

Muscular dystrophies (MDs) are a category of hereditary illnesses characterized by the gradual malfunction and/or weakening of the skeletal muscles. This disease of the muscles also results in hypotonia and joint contracture, along with raised serum creatine kinase (CK) levels. To prevent complications, continuous physiotherapy is advised for children with muscular dystrophy, which is even asked to perform at home as a home exercise program (HEP). As a result, the home exercise program (HEP) is critical in maintaining the optimal health of children with Duchenne muscular dystrophy (DMD). The present coronavirus (COVID-19) pandemic has adversely affected these children as there was very little scope to get direct help from a physiotherapist. Meanwhile, the home program was continued by many to compensate for the direct benefit. However, because of the lack of specific guidelines and structured methodology to follow for a home program, there was a deterioration in the health status of many children. There is a need to understand how the children are getting affected and the way the home program can be refined to help needy children with muscular dystrophy. Our scoping review aims to identify the present home program patterns being followed for children with DMD and their scope for refinement. The data were collected from electronic databases including PubMed, ProQuest, Cochrane, and Web of Science. We searched four electronic databases until September 2021. We included the published case studies, observational and experimental studies that described the positive impact of home exercise programs, and the methodology they followed as an alternative to institution-based physiotherapy. One hundred thirty-eight titles were screened, and 58 met the inclusion criteria. Along with regular physiotherapy, the incorporation of HEP helped in early complication prevention in patients with muscular dystrophy. The HEP was found to be a successful adjunct in the COVID-19 scenario. This review presents different therapeutic measures that can be taken for the prevention of complications in patients with MD and how the HEP plays an important role in removing the gaps on how HEP is beneficial in the COVID-19 scenario and a scope to refine the present methodologies for more accurate management.

Effect of COVID-19 lockdown on refractive errors in children aged 5-12 years: a retrospective study

Purpose : To explore whether the COVID-19 lockdown increased the incidence of myopia among age-school children. Methods : Retrospective study recruiting children aged 5-12. Selection: random. Inclusion criteria: healthy children presenting for an eye exam since 2016. Exclusion criteria: presence of ocular comorbidities other than refractive error, spherical equivalent (SE) less than -4D or greater than +4D, BCVA less than 20/20, blepharoptosis, media opacities, corneal or retinal dystrophies, strabismus, amblyopia, nystagmus, or concurrent therapy with atropine 0.01%. Outcome measure: age measured in months, SE of the right eye (RE) measured in diopters (D) under cycloplegia (cyclopentolate 1%). Statistical analysis: ANOVA, Chi-square, Tukey's test. Significance: p < .05. Results : A total of 803 children. In the years prior to COVID-19, the mean SE ± SD diopters in the RE: 0.54 ± 1.49 D in 2016 (n = 160), 0.43 ± 1.84 D in 2017 (n = 145), 0.34 ± 1.41 D in 2018 (n = 152), 0.35 ± 1.75 D in 2019 (n = 166) (ANOVA, p = .659) (Fig. 1). In 2021 (n = 180), the mean SE was -0.08 ± 1.44 D (ANOVA, p = .005). Using the Tukey's test, the mean SE of 2021 changed by -0.619 D 95% CI [-1.091, -0.147] and -0.501 D 95% CI [-0.986, -0.016] as compared to the SE of 2016 and 2017, respectively (Fig. 2). Mean age was comparable in all groups (ANOVA, p = .307). The decrease of the mean SE of the 2021 group corresponds to an increase in the percentage of myopes (≤-0.5D) and a decrease in the percentage of hyperopes (≥ 2D). Myopes represent the 24.10% of children aged 60-96 months, and 63.86% of children aged 97-144 months. Hyperopes represent 9.64% of children aged 60-96 months, and 6.02% of children aged 97-144 months. This represents a statistically-significant increase in the number of myopes (Chi-square, p = .016) and decrease in the number of hyperopes (Chi-square, p = .001), as compared to the previous years (2016- 2019). Conclusions : This retrospective study shows a statistically-significant decrease in the mean SE in children aged 5-12 in the year following the COVID-19 lockdown (2021). The percentage of myopes has increased significantly, while the percentage of hyperopes has decreased. Children aged 8-12 years showed the greatest refractive change. The lifestyle changes imposed by the lockdown were likely responsible for the increased prevalence of myopia observed in 2021.

Voretigene Neparvovec Exploratory Analysis (VNEAN): R-shiny app for the comprehensive and dynamic visualization of voretigene neparvovec clinical trial data

Purpose : R-shiny apps can be useful in maintaining and analyzing data collected in clinical trials of rare diseases, where a suite of measures is used to characterize retinal and visual function, functional vision, and safety courses over time following the treatment. In a phase 3 trial, participants with biallelic RPE65 mutation-associated inherited retinal dystrophy (IRD), an ultra-rare genetic disorder, received bilateral, subretinal injections of gene augmentation therapy, voretigene neparvovec and followed-up annually. We explored the development of a novel data visualization tool, VNEAN (R-shiny application), to help in maintenance and analyses of complex trial data into a visual storytelling form that is easier to understand for healthcare audience. Methods : We developed an interactive and dynamic application using Shiny package for R programming language. This app improves the ability to explore the longitudinal trajectory of main efficacy outcomes (mobility testing and full-field light sensitivity) in concert with other data, including visual function and safety that can be visualized overall and in subsets. Results : This app has 11 modules of data analyses (Figure 1), including longitudinal visualization, analyses of correlation between changes, and timeline of adverse events. It presents the durability in improvement of functional vision, retinal and visual function, and the safety data at the group, subset and participant levels. The dynamic interface allows the user to define a subset based on the measures at baseline and/or their changes and select measures and/or timepoints. Conclusions : COVID-19 demonstrated digital engagement at its peak. The R shiny app has the potential to provide alternative data visualization and interpretations of analyses that offer a comprehensive representation of the data generated in rare diseases, not easily achievable via traditional didactic lectures and static data methods. This patient-centric and enduring visualization approach enables health care professionals to learn and retain information for the management and engagement of IRD patients in their clinical practice. Additionally, this application can progress the knowledge and understanding of treatment effects of rare diseases and help inform the design of future small- or largescale trials.

CORNEAL GRAFT REJECTIONS DUE TO COVID 19 INFECTION OR VACCINATIONS : A CASE SERIES

Purpose : To report 4 cases of corneal graft rejections which occurred due to COVID19 infection or vaccination. Methods : Case 1 A 24-year old woman presented with corneal scar in her right eye (due to a resolved microbial keratitis) for which she underwent optical penetrating keratoplasty (PK). The patient presented with hyperacute endothelial rejection 5 weeks later. She had epithelial and endothelial corneal graft rejection (Figure 1) for which she was treated with intravenous methylprednisolone, along with topical steroids prescribed hourly and systemic steroids. 3 days later, she was diagnosed with COVID 19 infection. In spite of adequate treatment, her corneal graft could not be salvaged. Case 2 A 31-year old male who had history of chemical injury in the right eye in 2017, underwent second PK in 2020, and had graft rejection 4 weeks after 1st dose of COVID vaccine (COVISHIELD). He was successfully treated with hourly topical steroids along with systemic steroids and the corneal graft cleared up. Case 3 Another 29-year old male diagnosed with Macular corneal dystrophy underwent corneal transplantation in 2016 had graft rejection following 1st dose of COVID vaccine (COVISHIELD) 3 weeks later. The patient was treated with topical and systemic steroids. Though most part of the graft cleared up but inferior graft edema was found to persist (Figure 2). Case 4 A 17-year old girl, underwent PK for Congenital Hereditary Endothelial Dystrophy and had corneal graft rejection 1 month after the 2nd dose of COVID vaccine (COVISHIELD). With adequate treatment of topical and systemic steroids, the patient's corneal graft improved and cleared up, and the patient reports an improvement in visual acuity as well. Results :-Conclusions : COVID 19 infection and vaccination can induce graft rejection. Hyperacute endothelial rejection is possible with COVID 19 infection. COVID vaccine related corneal graft rejections may be less severe and may be reversed with adequate treatment.

Low-intensity Aerobic Exercises during COVID-19 Pandemic in Children with Duchenne Muscular Dystrophy: A Home based Study

Duchenne muscular dystrophy (DMD) is a rare genetic disorder that affects about 0.8 million Indian children. The incidence rate of 1:3500 male births is the most common form of all muscular dystrophies. Covid-19 pandemic cause profound devastation to the lives of DMD children. The muscles are weaker in DMD, and the children are more prone to lung infections. Coronavirus (COVID-19) is a severe lung infection that disturbs the entire function of the World. DMD already has weakness in major muscles, including the respiratory. So, the study aims to identity the effect of low-intensity aerobic exercises in children with DMD. This is a home-based pilot study with 11 DMD children and wheelchair dependent since, for ten years, they have been on continuous rehabilitation and monitoring. When the pandemic was declared in India in March 2020, all children were given clear notes on the disease and its severity to the parents. Self-created quarantine exercise protocol, which includes Limb exercises, breathing exercises, trunk mobility exercises, and positioning, was taught along with a logbook given to all the children. Video calls, and WhatsApp videos, were used to monitor them regularly. The physiotherapist made a personal visit in June 2020 to review the exercises, and subsequently on Aug 20, Oct 20, Dec 20, Feb 21, and May 21. Observations are detailed here. The infection rate was 3 out of 9, and they got admitted to the hospital for other illnesses. All the children noted Flu infection but recovered within ten days without hospitalization. The parents monitored their SPo2 and temperature and updated them in the logbook. A lung function test was done using a handheld incentive spirometer during the personnel visit by the therapist and found satisfactory. The study concluded a significant improvement in the DMD children following low-intensity and quarantine exercises.