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Molecular Diagnosis & Therapy Jan 2022Achromatopsia (ACHM), also known as rod monochromatism or total color blindness, is an autosomal recessively inherited retinal disorder that affects the cones of the... (Review)
Review
Achromatopsia (ACHM), also known as rod monochromatism or total color blindness, is an autosomal recessively inherited retinal disorder that affects the cones of the retina, the type of photoreceptors responsible for high-acuity daylight vision. ACHM is caused by pathogenic variants in one of six cone photoreceptor-expressed genes. These mutations result in a functional loss and a slow progressive degeneration of cone photoreceptors. The loss of cone photoreceptor function manifests at birth or early in childhood and results in decreased visual acuity, lack of color discrimination, abnormal intolerance to light (photophobia), and rapid involuntary eye movement (nystagmus). Up to 90% of patients with ACHM carry mutations in CNGA3 or CNGB3, which are the genes encoding the alpha and beta subunits of the cone cyclic nucleotide-gated (CNG) channel, respectively. No authorized therapy for ACHM exists, but research activities have intensified over the past decade and have led to several preclinical gene therapy studies that have shown functional and morphological improvements in animal models of ACHM. These encouraging preclinical data helped advance multiple gene therapy programs for CNGA3- and CNGB3-linked ACHM into the clinical phase. Here, we provide an overview of the genetic and molecular basis of ACHM, summarize the gene therapy-related research activities, and provide an outlook for their clinical application.
Topics: Animals; Color Vision Defects; Cyclic Nucleotide-Gated Cation Channels; Genetic Therapy; Humans; Mutation; Retinal Cone Photoreceptor Cells
PubMed: 34860352
DOI: 10.1007/s40291-021-00565-z -
The New England Journal of Medicine Dec 2019Ubrogepant is an oral, small-molecule calcitonin gene-related peptide receptor antagonist for acute migraine treatment. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Ubrogepant is an oral, small-molecule calcitonin gene-related peptide receptor antagonist for acute migraine treatment.
METHODS
We conducted a randomized trial to evaluate the efficacy, safety, and side-effect profile of ubrogepant. We assigned adults with migraine, with or without aura, in a 1:1:1 ratio to receive an initial dose of placebo, ubrogepant at a dose of 50 mg, or ubrogepant at a dose of 100 mg for treatment of a single migraine attack, with the option to take a second dose. The coprimary efficacy end points were freedom from pain at 2 hours after the initial dose and absence of the most bothersome migraine-associated symptom at 2 hours. Secondary end points included pain relief (at 2 hours), sustained pain relief (from 2 to 24 hours), sustained freedom from pain (from 2 to 24 hours), and absence of symptoms associated with migraine (photophobia, phonophobia, and nausea) at 2 hours.
RESULTS
A total of 1672 participants were enrolled; 559 were assigned to receive placebo, 556 to receive 50 mg of ubrogepant, and 557 to receive 100 mg of ubrogepant. The percentage of participants who had freedom from pain at 2 hours was 11.8% in the placebo group, 19.2% in the 50-mg ubrogepant group (P = 0.002, adjusted for multiplicity, for the comparison with placebo), and 21.2% in the 100-mg ubrogepant group (P<0.001). The percentage of participants who had freedom from the most bothersome symptom at 2 hours was 27.8% in the placebo group, 38.6% in the 50-mg ubrogepant group (P = 0.002), and 37.7% in the 100-mg ubrogepant group (P = 0.002). Adverse events within 48 hours after the initial or optional second dose were reported in 12.8% of participants in the placebo group, in 9.4% in the 50-mg ubrogepant group, and in 16.3% in the 100-mg ubrogepant group. The most common adverse events were nausea, somnolence, and dry mouth (reported in 0.4 to 4.1%); these events were more frequent in the 100-mg ubrogepant group (reported in 2.1 to 4.1%). Serious adverse events reported within 30 days in the ubrogepant groups included appendicitis, spontaneous abortion, pericardial effusion, and seizure; none of the events occurred within 48 hours after the dose.
CONCLUSIONS
A higher percentage of participants who received ubrogepant than of those who received placebo had freedom from pain and absence of the most bothersome symptom at 2 hours after the dose. The most commonly reported adverse events were nausea, somnolence, and dry mouth. Further trials are needed to determine the durability and safety of ubrogepant for acute migraine treatment and to compare it with other drugs for migraine. (Funded by Allergan; ClinicalTrials.gov number, NCT02828020.).
Topics: Adult; Calcitonin Gene-Related Peptide Receptor Antagonists; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Hyperacusis; Kaplan-Meier Estimate; Male; Migraine Disorders; Nausea; Pain Management; Photophobia; Pyridines; Pyrroles
PubMed: 31800988
DOI: 10.1056/NEJMoa1813049 -
Journal Francais D'ophtalmologie Sep 2020Cataract is a partial or total opacification of the crystalline lens. In adults, cataract is acquired; the most common form is the age-related cataract. Assessment of... (Review)
Review
Cataract is a partial or total opacification of the crystalline lens. In adults, cataract is acquired; the most common form is the age-related cataract. Assessment of the functional impact of a cataract is clinical. The common symptom is loss of visual acuity, but other symptoms (photophobia, monocular diplopia, myopic shift, change in color vision, etc.) may be found depending on the anatomical distribution of the opacities (nuclear, posterior subcapsular, cortical). Diagnosis is based on slit-lamp examination after pupillary dilation. This allows classification of the opacities according to their anatomical distribution and can help direct any etiologic work-up. A number of potential causes should be ruled out before concluding that a cataract is age-related. Cataracts may be iatrogenic, associated with other ocular or systemic disease, or induced by ocular trauma. Knowledge of the signs, symptoms, and clinical forms of cataract helps to establish proper indications for cataract surgery in accordance with preferred practice patterns in ophthalmology.
Topics: Adult; Age of Onset; Cataract; Humans; Prevalence; Visual Acuity
PubMed: 32586638
DOI: 10.1016/j.jfo.2019.11.009 -
Ugeskrift For Laeger Nov 2023This is a case report of a 3-year-old boy who presented with unilateral anterior uveitis and tonic pupil following varicella-zoster virus (VZV) Infection. The patient...
This is a case report of a 3-year-old boy who presented with unilateral anterior uveitis and tonic pupil following varicella-zoster virus (VZV) Infection. The patient had red and irritated eyes and photophobia. Ophthalmological findings included anterior uveitis and tonic pupil accompanied by reduced vision and accommodation. An MRI of the cerebrum was normal. To ease the symptoms the patient was prescribed photophobia glasses with correction of hyperopia. Tonic pupil due to VZV infection is a rare complication, but may have long-term consequences, why patients with eye-involving VZV infection need to be examined by an ophthalmologist.
Topics: Male; Humans; Child; Child, Preschool; Chickenpox; Tonic Pupil; Photophobia; Herpesvirus 3, Human; Uveitis, Anterior; Acute Disease
PubMed: 38018730
DOI: No ID Found