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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 -
JAMA Ophthalmology Jun 2017Some uncertainty about the clinical value and dosing of atropine for the treatment of myopia in children remains. (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
Some uncertainty about the clinical value and dosing of atropine for the treatment of myopia in children remains.
OBJECTIVE
To evaluate the efficacy vs the adverse effects of various doses of atropine in the therapy for myopia in children.
DATA SOURCES
Data were obtained from PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials, from inception to April 30, 2016. The reference lists of published reviews and clinicaltrials.gov were searched for additional relevant studies. Key search terms included myopia, refractive errors, and atropine. Only studies published in English were included.
STUDY SELECTION
Randomized clinical trials and cohort studies that enrolled patients younger than 18 years with myopia who received atropine in at least 1 treatment arm and that reported the annual rate of myopia progression and/or any adverse effects of atropine therapy were included in the analysis.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently abstracted the data. Heterogeneity was statistically quantified by Q, H, and I2 statistics, and a meta-analysis was performed using the random-effects model. The Cochrane Collaboration 6 aspects of bias and the Newcastle-Ottawa Scale were used to assess the risk for bias.
MAIN OUTCOMES AND MEASURES
The primary outcome was a difference in efficacy and the presence of adverse effects at different doses of atropine vs control conditions. The secondary outcomes included the differences in adverse effects between Asian and white patients.
RESULTS
Nineteen unique studies involving 3137 unique children were included in the analysis. The weighted mean differences between the atropine and control groups in myopia progression were 0.50 diopters (D) per year (95% CI, 0.24-0.76 D per year) for low-dose atropine, 0.57 D per year (95% CI, 0.43-0.71 D per year) for moderate-dose atropine, and 0.62 D per year (95% CI, 0.45-0.79 D per year) for high-dose atropine (P < .001), which translated to a high effect size (Cohen d, 0.97, 1.76, and 1.94, respectively). All doses of atropine, therefore, were equally beneficial with respect to myopia progression (P = .15). High-dose atropine were associated with more adverse effects, such as the 43.1% incidence of photophobia compared with 6.3% for low-dose atropine and 17.8% for moderate-dose atropine (χ22 = 7.05; P = .03). In addition, differences in the incidence of adverse effects between Asian and white patients were not identified (χ21 = 0.81; P = .37 for photophobia).
CONCLUSIONS AND RELEVANCE
This meta-analysis suggests that the efficacy of atropine is dose independent within this range, whereas the adverse effects are dose dependent.
Topics: Atropine; Child; Disease Progression; Dose-Response Relationship, Drug; Humans; Mydriatics; Myopia; Refraction, Ocular
PubMed: 28494063
DOI: 10.1001/jamaophthalmol.2017.1091 -
Journal of Neuro-ophthalmology : the... Mar 2019Photophobia is commonly associated with migraine, meningitis, concussion, and a variety of ocular diseases. Advances in our ability to trace multiple brain pathways... (Review)
Review
BACKGROUND
Photophobia is commonly associated with migraine, meningitis, concussion, and a variety of ocular diseases. Advances in our ability to trace multiple brain pathways through which light information is processed have paved the way to a better understanding of the neurobiology of photophobia and the complexity of the symptoms triggered by light.
PURPOSE
The purpose of this review is to summarize recent anatomical and physiological studies on the neurobiology of photophobia with emphasis on migraine.
RECENT FINDINGS
Observations made in blind and seeing migraine patients, and in a variety of animal models, have led to the discovery of a novel retino-thalamo-cortical pathway that carries photic signal from melanopsinergic and nonmelanopsinergic retinal ganglion cells (RGCs) to thalamic neurons. Activity of these neurons is driven by migraine and their axonal projections convey signals about headache and light to multiple cortical areas involved in the generation of common migraine symptoms. Novel projections of RGCs into previously unidentified hypothalamic neurons that regulate parasympathetic and sympathetic functions have also been discovered. Finally, recent work has led to a novel understanding of color preference in migraine-type photophobia and of the roles played by the retina, thalamus, and cortex.
SUMMARY
The findings provide a neural substrate for understanding the complexity of aversion to light in patients with migraine and neuro-ophthalmologic other disorders.
Topics: Animals; Cerebral Cortex; Humans; Migraine Disorders; Neural Pathways; Photophobia; Retinal Ganglion Cells; Thalamus
PubMed: 30762717
DOI: 10.1097/WNO.0000000000000766 -
Journal of Clinical Virology : the... Sep 2017Aseptic meningitis represents a common diagnostic and management dilemma to clinicians.
BACKGROUND
Aseptic meningitis represents a common diagnostic and management dilemma to clinicians.
OBJECTIVES
To compare the clinical epidemiology, diagnostic evaluations, management, and outcomes between adults and children with aseptic meningitis.
STUDY DESIGN
We conducted a retrospective study from January 2005 through September 2010 at 9 Memorial Hermann Hospitals in Houston, TX. Patients age≥2months who presented with community-acquired aseptic meningitis with a CSF white blood cell count >5cells/mm and a negative Gram stain and cultures were enrolled. Patients with a positive cryptococcal antigen, positive blood cultures, intracranial masses, brain abscesses, or encephalitis were excluded.
RESULTS
A total of 509 patients were included; 404 were adults and 105 were children. Adults were most likely to be female, Caucasian, immunosuppressed, have meningeal symptoms (headache, nausea, stiff neck, photophobia) and have a higher CSF protein (P <0.05). In contrast, children were more likely to have respiratory symptoms, fever, and leukocytosis (P <0.05). In 410 (81%) patients, the etiologies remained unknown. Adults were more likely to be tested for and to have Herpes simplex virus and West Nile virus while children were more likely to be tested for and to have Enterovirus (P <0.001). The majority of patients were admitted (96.5%) with children receiving antibiotic therapy more frequently (P <0.001) and adults receiving more antiviral therapy (P=0.001). A total of 384 patients (75%) underwent head CT scans and 125 (25%) MRI scans; all were normal except for meningeal enhancement. All patients had a good clinical outcome at discharge.
DISCUSSION
Aseptic meningitis in adults and children represent a management challenge as etiologies remained unknown for the majority of patients due to underutilization of currently available diagnostic techniques.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Female; Hospitalization; Humans; Infant; Infant, Newborn; Male; Meningitis, Aseptic; Middle Aged; Retrospective Studies; Texas; Young Adult
PubMed: 28806629
DOI: 10.1016/j.jcv.2017.07.016 -
Annals of Indian Academy of Neurology Apr 2018Hemicrania continua (HC) is an indomethacin responsive primary chronic headache disorder which is currently classified as a subtype of trigeminal autonomic cephalalgias... (Review)
Review
Hemicrania continua (HC) is an indomethacin responsive primary chronic headache disorder which is currently classified as a subtype of trigeminal autonomic cephalalgias (TACs). It is not very uncommon. There are >1000 cases of HC in the literature, and it constitutes 1.7% of total headache in the clinic settings. Misdiagnosis for HC is very common at all clinical settings. A diagnosis of HC is missed even by neurologists and headache specialists. It is characterized by a continuous strictly unilateral headache with superimposed exacerbations. Just like other TACs, exacerbations are associated with cranial autonomic symptoms and restlessness. A large number of patients may have migrainous features (nausea, vomiting, photophobia, and phonophobia) during exacerbations phase. The "key" feature of HC is persistent featureless background headaches. However, patients and physicians may focus only on the exacerbation part. As durations, frequency and associated symptoms of exacerbations are highly variables; it may mimic a large number of primary and secondary headache disorders. Migraine and cluster headache are two most common misdiagnosed conditions. Another specific feature of HC is remarkable repose to indomethacin. A "complete" response to indomethacin is as "sine qua non" for HC. However, a few other medications may also be effective in a subset of HC patients. Various surgical procedures have been tried with mixed results in patients who were intolerant to indomethacin or other drugs.
PubMed: 29720815
DOI: 10.4103/aian.AIAN_352_17