Clinical features and possible pathogenesis of multiple evanescent white dot syndrome with different retinal diseases and events:a narrative review

●Multiple evanescent white dot syndrome(MEWDS)is a rare fundus disease,characterized by acute vision loss and visual field defects.Many previous studies have explained the possible pathogenesis and clinical features of primary MEWDS.However,as the number of reported cases increases,secondary MEWDS occurs in other related retinal diseases and injuries,exhibiting some special characteristics.The associated retinal diseases include multifocal choroiditis/punctate inner choroidopathy(MFC/PIC),acute zonal occult outer retinopathy,best vitelliform macular dystrophy,pseudoxanthoma elasticum,and ocular toxoplasmosis.The related retinal injury is laser photocoagulation,surgery,and trauma.Although primary MEWDS often have a self-limiting course,secondary MEWDS may require treatment in some cases,according to the severity of concomitant diseases and complications.Notably,MEWDS secondary to MFC/PIC that is prone to forming choroidal neovascularization and focal choroidal excavation,needs positive treatment with corticosteroids.The possible underlying pathogenesis of secondary MEWDS is the exposure of choroidal antigen after the disruption of Bruch’s membrane.The MEWDS-related features in secondary MEWDS are still evanescent under most circumstances.Its prognosis and treatment depend on the severity of complications.Current studies propose that the etiology is associated with immune factors,including viral infection,inflammation in choroid and Bruch’s membrane,and antigen exposure caused by retinal and/or choroidal insults.More pathogenic studies should be conducted in the future.Accurate diagnosis for secondary MEWDS could benefit patients in aspects of management and prognosis.

Laser confocal microscopy findings of Thygeson superficial punctate keratitis

Thygeson superficial punctate keratitis （TSPK） is a rare,chronic,inflammatory disorder,with adverse impact on the visual function and quality of life in patients.It was first described by Thygeson in 1950,1 as typically bilateral,corneal epithelial opacities without associated stromal involvement or corneal edema.Recurrent episodes of tearing,foreign body sensation,photophobia,and reduced vision are observed.To date,virus infection and immune factors have been considered as important risk factors for visual deterioration in the patients with TSPK,but the origin of the comeal opacities remains poorly understood.Keywords：Thygeson superficial punctate keratitis ; laser confocal microscopy

Assessment of cheese sign and its association with vascular risk factors:Data from PUMCH dementia cohort

Background:In the clinic,practitioners encounter many patients with an abnormal pattern of dense punctate magnetic resonance imaging(MRI)signal in the basal ganglia,a phenomenon known as"cheese sign".This sign is reported as common in cerebrovascular diseases,dementia,and old age.Recently,cheese sign has been speculated to consist of dense perivascular space(PVS).This study aimed to assess the lesion types of cheese sign and analyze the correlation between this sign and vascular disease risk factors.Methods:A total of 812 patients from Peking Union Medical College Hospital(PUMCH)dementia cohort were enrolled.We analyzed the relationship between cheese sign and vascular risk.For assessing cheese sign and defining its degree,the abnormal punctate signals were classified into basal ganglia hyperintensity(BGH),PVS,lacunae/infarctions and microbleeds,and counted separately.Each type of lesion was rated on a four-level scale,and then the sum was calculated;this total was defined as the cheese sign score.Fazekas and Age-Related White Matter Changes(ARWMC)scores were used to evaluate the paraventricular,deep,and subcortical gray/white matter hyperintensities.Results:A total of 118 patients(14.5%)in this dementia cohort were found to have cheese sign.Age(odds ratio[OR]:1.090,95%confidence interval[CI]:1.064-1.120,P<0.001),hypertension(OR:1.828,95%CI:1.123-2.983,P=0.014),and stroke(OR:1.901,95%CI:1.092-3.259,P=0.025)were risk factors for cheese sign.There was no significant relationship between diabetes,hyperlipidemia,and cheese sign.The main components of cheese sign were BGH,PVS,and lacunae/infarction.The proportion of PVS increased with cheese sign severity.Conclusions:The risk factors for cheese sign were hypertension,age,and stroke.Cheese sign consists of BGH,PVS,and lacunae/infarction.

Microglial Depletion does not Afect the Laterality of Mechanical Allodynia in Mice

Mechanical allodynia(MA),including punctate and dynamic forms,is a common and debilitating symptom suffered by millions of chronic pain patients.Some peripheral injuries result in the development of bilateral MA,while most injuries usually led to unilateral MA.To date,the control of such laterality remains poorly understood.Here,to study the role of microglia in the control of MA laterality,we used genetic strategies to deplete microglia and tested both dynamic and punctate forms of MA in mice.Surprisingly,the depletion of central microglia did not prevent the induction of bilateral dynamic and punctate MA.Moreover,in dorsal root ganglion-dorsal root-sagittal spinal cord slice preparations we recorded the low-threshold Aβ-fiber stimulation-evoked inputs and outputs of superficial dorsal horn neurons.Consistent with behavioral results,microglial depletion did not prevent the opening of bilateral gates for Aβpathways in the superficial dorsal horn.This study challenges the role of microglia in the control of MA laterality in mice.Future studies are needed to further understand whether the role of microglia in the control of MA laterality is etiology-or species-specific.

Targeting Peripheral μ-opioid Receptors or μ-opioid Receptor-Expressing Neurons Does not Prevent Morphine-induced Mechanical Allodynia and Anti-allodynic Tolerance

The chronic use of morphine and other opioids is associated with opioid-induced hypersensitivity(OIH)and analgesic tolerance.Among the different forms of OIH and tolerance,the opioid receptors and cell types mediating opioid-induced mechanical allodynia and anti-allodynic tolerance remain unresolved.Here we demonstrated that the loss of peripheralμ-opioid receptors(MORs)or MOR-expressing neurons attenuated thermal tolerance,but did not affect the expression and maintenance of morphine-induced mechanical allodynia and anti-allodynic tolerance.To confirm this result,we made dorsal root ganglia-dorsal roots-sagittal spinal cord slice preparations and recorded low-threshold Aβ-fiber stimulation-evoked inputs and outputs in superficial dorsal horn neurons.Consistent with the behavioral results,peripheral MOR loss did not prevent the opening of Aβmechanical allodynia pathways in the spinal dorsal horn.Therefore,the peripheral MOR signaling pathway may not be an optimal target for preventing mechanical OIH and analgesic tolerance.Future studies should focus more on central mechanisms.