Spectrum of digoxin-induced ocular toxicity: a case report and literature review

BACKGROUND: Digoxin intoxication results in predominantly digestive, cardiac and neurological symptoms. This case is outstanding in that the intoxication occurred in a nonagenarian and induced severe, extensively documented visual symptoms as well as dysphagia and proprioceptive illusions. Moreover, it went undiagnosed for a whole month despite close medical follow-up, illustrating the difficulty in recognizing drug-induced effects in a polymorbid patient. CASE PRESENTATION: Digoxin 0.25 mg qd for atrial fibrillation was prescribed to a 91-year-old woman with an estimated creatinine clearance of 18 ml/min. Over the following 2-3 weeks she developed nausea, vomiting and dysphagia, snowy and blurry vision, photopsia, dyschromatopsia, aggravated pre-existing formed visual hallucinations and proprioceptive illusions. She saw her family doctor twice and visited the eye clinic once until, 1 month after starting digoxin, she was admitted to the emergency room. Intoxication was confirmed by a serum digoxin level of 5.7 ng/ml (reference range 0.8-2 ng/ml). After stopping digoxin, general symptoms resolved in a few days, but visual complaints persisted. Examination by the ophthalmologist revealed decreased visual acuity in both eyes, 4/10 in the right eye (OD) and 5/10 in the left eye (OS), decreased color vision as demonstrated by a score of 1/13 in both eyes (OU) on Ishihara pseudoisochromatic plates, OS cataract, and dry age-related macular degeneration (ARMD). Computerized static perimetry showed non-specific diffuse alterations suggestive of either bilateral retinopathy or optic neuropathy. Full-field electroretinography (ERG) disclosed moderate diffuse rod and cone dysfunction and multifocal ERG revealed central loss of function OU. Visual symptoms progressively improved over the next 2 months, but multifocal ERG did not. The patient was finally discharged home after a 5 week hospital stay. CONCLUSION: This case is a reminder of a complication of digoxin treatment to be considered by any treating physician. If digoxin is prescribed in a vulnerable patient, close monitoring is mandatory. In general, when facing a new health problem in a polymorbid patient, it is crucial to elicit a complete history, with all recent drug changes and detailed complaints, and to include a drug adverse reaction in the differential diagnosis

Transcriptomic Signature Differences Between SARS-CoV-2 and Influenza Virus Infected Patients.

The reason why most individuals with COVID-19 have relatively limited symptoms while other develop respiratory distress with life-threatening complications remains unknown. Increasing evidence suggests that COVID-19 associated adverse outcomes mainly rely on dysregulated immunity. Here, we compared transcriptomic profiles of blood cells from 103 patients with different severity levels of COVID-19 with that of 27 healthy and 22 influenza-infected individuals. Data provided a complete overview of SARS-CoV-2-induced immune signature, including a dramatic defect in IFN responses, a reduction of toxicity-related molecules in NK cells, an increased degranulation of neutrophils, a dysregulation of T cells, a dramatic increase in B cell function and immunoglobulin production, as well as an important over-expression of genes involved in metabolism and cell cycle in patients infected with SARS-CoV-2 compared to those infected with influenza viruses. These features also differed according to COVID-19 severity. Overall and specific gene expression patterns across groups can be visualized on an interactive website (https://bix.unil.ch/covid/). Collectively, these transcriptomic host responses to SARS-CoV-2 infection are discussed in the context of current studies, thereby improving our understanding of COVID-19 pathogenesis and shaping the severity level of COVID-19

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Œdème maculaire microkystique : une complication fréquente des neuropathies optiques

L'œdème maculaire microkystique (OMM) est une entité définie comme un œdème non exsudatif de la rétine avec des zones lacunaires cystoïdes hyporéflectives situées dans la couche nucléaire interne de la rétine. Il est facilement mis en évidence par la tomographie à cohérence optique de haute définition (OCT) et a été décrit initialement en 2012 dans les névrites optiques associées à des maladies démyélinisantes. Le but de notre premier article publié en 2015 (Klin Monbl Augenheilkd. 2015 Apr;232(4):455-8) a été de décrire cliniquement une série de cas de neuropathies optiques et de montrer que ce type d'œdème n'était pas rencontré uniquement dans les atteintes inflammatoires du nerf optique, mais également dans d'autres étiologies (compressive, glaucomateuse, ischémique, traumatique, dégénérative et héréditaire). Nous avons recherché une éventuelle corrélation entre la localisation de l'OMM et les déficits campimétriques secondaires à l'atrophie optique. Cette corrélation s'est avérée positive dans 26% des cas uniquement. De cette série clinique, nous avons pu conclure que l'OMM était une manifestation non spécifique de neuropathie optique d'origine variée, sans prédilection de genre et que le phénomène physiopathologique sous-jacent restait encore inconnu. Le second article, écrit en collaboration avec les Drs Abegg et Dysli de l'Inselspital à Berne, publié en mars 2018 (Eur Neurol. 2018;79(3-4):150-153), visait quant à lui à étudier l'éventuelle efficacité du traitement d'acétazolamide dans les cas d'OMM secondaires à des neuropathies optiques. L'une des hypothèses physiopathologiques conduisant à l'OMM serait une dysfonction de l'assèchement rétinien par les cellules de soutien de Muller. Cette altération serait secondaire à la perte de cellules ganglionnaires de la rétine, résultant d'une neuropathie optique. L'acétazolamide agit sur le transport aqueux cellulaire. Dans notre étude, l'acétazolamide s'est avéré efficace pour diminuer significativement l'épaisseur de l'OMM dans les yeux atteints, sans effet secondaire notable. Cependant, l'amélioration anatomique de la rétine (visualisable par OCT in vivo) ne s'est, quant à elle, pas associée à une récupération fonctionnelle visuelle significative. Cette absence d'amélioration de la fonction visuelle est explicable par le fait que la perte de fonction visuelle soit primairement liée à l'appauvrissement des cellules ganglionnaires (neuropathie optique) et non à la présence d'un épaississement rétinien au niveau de la macula. En conclusion, l'OMM est une entité que l'on rencontre en association avec environ 8-10% des neuropathies optiques de multiples étiologies. Le mécanisme physiopathologique sous- jacent reste à prouver, mais la dysfonction du transport aqueux des cellules de Muller semble plausible, car cet œdème répond au traitement d'acétazolamide, sans pour autant améliorer le devenir visuel des patients qui en sont atteint

Spontaneous consecutive esotropia.

Although less frequent than consecutive exotropia, consecutive esotropia is a well-known type of strabismus when it follows the surgical correction of an exotropia. Spontaneous conversion from initial constant, large-angle exotropia beyond the age of 3 months to esotropia or orthophoria, however, is not common. We describe a series of infants who presented a spontaneous evolution from a large-angle infantile exotropia to either an orthophoria or a spontaneously consecutive esotropia. Cases of infants examined in the pediatric neuro-ophthalmology clinic of a tertiary ophthalmology department between 2009 and 2015, and having presented an early large-angle exotropia that spontaneously converted into an esotropia or orthophoria-i.e., without any previous surgery or botulinum toxin injection-were studied. Ten cases (6 M:4 F) were followed up. Median age at first exotropia assessment was 3.88 months (SD = 6.35). Median age at spontaneous conversion to esotropia or orthophoria was 7.23 months (SD = 14.73). Six patients suffered from severe neurologic or metabolic diseases, three had neonatal respiratory distress syndrome, and one was healthy. Spontaneous conversion from initial large-angle exotropia to esotropia or orthophoria can be encountered. The cerebral maturation of visual structures probably accounts for this uncommon strabismus sequence