Objective To provide detailed clinical and molecular genetic findings and describe the characteristics of natural history in Chinese choroideremia (CHM) patients.Methods The patients with CHM who met the inclusion criteria of at least two visits over a minimum period of 5 years were recruited on a voluntary basis at the Ophthalmic Genetics Clinic in Peking Union Medical College Hospital from April 2009 to August 2017.Molecular genetic analysis results,best-corrected visual acuity (BCVA),color fundus photograph,optical coherence tomography (OCT),visual field (VF),full-field electroretinography (fERG) were obtained.This study protocol was approved by the Institutional Review Board of Peking Union Medical College Hospital (S-K125).Written informed consent was obtained from each participant.Results Ten Chinese Han patients from seven CHM families were included.The mutations were confirmed by molecular genetic analysis,and two novel mutations were found.The median age of 10 patients at first visit was 44 years (range 8-52 years).The mean first-last visit period was 6.08 years (range 5.03-7.24 years).The mean BCVA at first visit in logMAR equivalents was 0.56 (range 0.0-2.0) or approximately 0.28 decimal acuity.The correlation between BCVA at first visit and age showed that relative good vision remained until 35 years old and BCVA subsequently reduced rapidly.OCT showed a thickening of the central retinal thickness at early stage,followed by a thinning over decades.Outer retinal tabulation (ORT) was shown in some patients.There was a strong negative correlation (r=-0.861,P＜0.001) between residual VF and age.Five patients did not need to record fERG because of serious fundus lesions.Two patients exhibited decreased amplitudes for both rod and cone-driven responses,and three patients exhibited no fERG amplitudes.Conclusions The progression of CHM may be severer and faster in Chinese patients than that in Western patients.ORT is an important manifestation of OCT in CHM patients.VF and fERG are applicable to evaluate the condition of very-early phase of CHM.

Objective To analyze the clinical features of cancer-associated retinopathy (CAR).Methods The clinical data of 10 patients who diagnosed as CAR during 5 years were retrospectively analyzed.All patients underwent detailed ocular examinations,including electroretinogram (ERG),optical coherence tomography (OCT),visual field (VF) and autofluorescence(AF).Results The primary malignancy was lung carcinoma in 3 patients,thymoma in 3 patients,thyroid carcinoma in 1 patients,maxillary sinus tumor in 1 patients,nasopharyngeal carcinoma in 1 patients and rectal cancer in 1 patients.All patients complained progressive visual reducing.Three patients manifested night blindness.The best corrected visual acuity (BCVA)＜0.1 was in three eyes,≤0.1-＜0.5 in seven eyes,and ≥0.5 in ten eyes.Patients showed normal fundi or mild abnormality.OCT images showed disorganization and/or loss of the ellipsoid zone in the macular area in 4 patients,and other six patients had only central foveal ellipsoid zone preserved.Eight patients had moderately or severely reduced ffERG,and 2 patients demonstrated electro-negative ERG.Five patients revealed peripheral visual defect.AF images were from normal to low or high AF patches in the posterior pole and mid-peripheral retina.Conclusions The clinical manifestations of CAR are varied as common characteristics of progressive visual decrease with or without night blindness,visual field defect and abnormal ffERG recording.

Objective:To access the genetic defects and clinical characteristics of patients with KCNV2-associated cone dystrophy. Methods:Three pedigrees with KCNV2-associated cone dystrophy were recruited in Peking Union Medical College Hospital from August 2017 to December 2019.Peripheral blood from each patient and their parents was collected, and genomic DNA was extracted.Targeted exome capture plus next-generation sequencing (NGS) was used to detect the candidate variants.Suspected causative variants were validated by Sanger sequencing and segregation analysis.Comprehensive ocular examinations were performed, including vision acuity, colour vision, fundus photography, fundus autofluorescence (FAF), optical coherence tomography (OCT), visual field and electroretinogram (ERG). This study was approved by the Institutional Review Board of Peking Union Medical College Hospital and adhered to the tenets of the Declaration of Helsinki.Written informed consent was obtained from each patient prior to any medical examination. Results:Three probands from three unrelated Chinese families were confirmed carrying biallelic KCNV2 disease-causing variants.Two patients harbored compound heterozygous variants and one patient with history of consanguinity was identified carrying homozygous variant.Five novel variants in the KCNV2 gene were identified, including p. T121M, p.R244C, p.C199Y, p.M250R and p. L171Pfs*201.All patients enrolled in this study were male with age of 25, 16 and 2 years old, respectively.Three affected individuals complained of vision loss and photophobia and two patients demonstrated reduced color perception and nystagmus.Macular discoloration (bull's eye maculopathy or gold foil macular reflex) was observed in fundus photographs.Macular hypofluorescence was illustrated in FAF imaging, which accompanying a broad hyperfluorescent ring surrounding the central atrophy or not.Macular thinning with loss of the inner segment ellipsoid zone was noted in OCT images, and the disruption was more profound in older patients.Central scotoma with or without peripheral visual field defects was observed in perimetry.Severe cone function loss and variable scotopic rod impairment were demonstrated in ERG, whereas a broad a-wave trough response to scotopic bright flash stimulation was noted. Conclusions:Patients with KCNV2-associated cone dystrophy show a characteristic ERG manifestation.ERG results and KCNV2 variants in Chinese patients differ from those in foreigners.

Objective:To identify the clinical characteristics and pathogenic gene of a Chinese Han family with achromatopsia (ACHM).Methods:The method of pedigree investigation was adopted.A Chinese Han ACHM family was recruited in Peking Union Medical College Hospital form July 2010 to July 2019, including 5 members of 2 generations.There were 2 patients and 3 phenotypically normal individuals.The medical history was collected and comprehensive ophthalmic examinations were performed, including visual acuity, colour vision, color fundus photography, fundus autofluorescence (FAF), optical coherence tomography (OCT), visual field and electroretinogram (ERG).Genomic DNA was extracted from peripheral blood sample from the patients and family members.Pathogenic variant was screened by whole exome sequencing (WES) and verified by Sanger sequencing and co-segregation analysis.The variant was annotated with the 1000 Genomes, Human Gene Mutation Database (HGMD), ExAC, ClinVar and OMIM databases to detect the single nucleotide polymorphism and whether it had been reported previously.The pathogenicity of the variant was evaluated according to the standards and guidelines of the American College of Medical Genetics and Genomics (ACMG).This study adhered to the Declaration of Helsinki.The study protocol was approved by the Institutional Review Board of Peking Union Medical College Hospital (No.JS-2059).Written informed consent was obtained from the guardians of juvenile patients.Results:There was consanguinity between the proband's parents and this family was consistent with autosomal recessive inheritance.Both male patients presented the reduction of visual acuity accompanied with photophobia and color blindness since childhood.Barely visible foveal light reflex in fundus images, hypofluorescence of foveal areas in FAF images, foveal defect with disruption of ellipsoid zone and interdigitation zone in OCT images were found in both patients.Central scotoma with or without peripheral visual field defects was detected.Generally normal scotopic 0.01, 3.0 and 10.0 responses, decreased oscillatory potentials amplitudes, no photopic 3.0 and 30 Hz flicker responses were observed.No sign of progression was found during the 9-year follow-up.It was confirmed that both patients carried a novel homozygous disease-causing variant c. 947insA (p.Asn316Lysfs*46) in ATF6 gene.Their mother had the heterozygous variant.The unaffected brother did not carry the variant.This family was consistent with co-segregation.This variant was labeled as pathogenic according to the ACMG standards and guidelines. Conclusions:A novel variant c.947insA (p.Asn316Lysfs*46) in ATF6 gene is the pathogenic variant of this achromatopsia family.This is the first time that this variant has been reported.

Objective:To assess the shielding requirements of low energy X-ray intraoperative radiotherapy room under the domestic and foreign standards and guidelines, to measure the sured transmission factors for a range of shielding materials, the ambient dose equivalent rate around concerned positions and the shielding effect of protective devices, so as to provide references for shielding design of such radiotherapy units and applications of radiological protection devices.Methods:The required shielding thicknesses for a treatment room with INTRABEAM intraoperative radiotherapy system were calculated under the Chinese national standard GBZ 121, IPEM report No. 75 and NCRP report No. 151, respectively. The transmission factors for a range of shielding materials including solid water slab, shielding sheet and shielding apron were measured. Moreover, the ambient dose equivalent rates were measured under the simulated working conditions and the shielding effectiveness of a lead screen was evaluated.Results:The required lead thicknesses calculated under different standards and guidelines were less than 0.6 mm for all the concerned points, with the differences at sub-millimeter level. The low energy X-rays generated by this equipment attenuated rapidly in the shielding materials. The measured transmission factors of 0.05 mm lead equivalent shielding sheet and 0.25 mm lead equivalent shielding apron were 0.068 and 0.003 8, respectively. When the radiation was delivered using spherical applicator without any attenuation, the ambient dose equivalent rates at 1 m and 2 m from the X-ray source were 10.7 and 2.6 mSv/h, respectively. The corresponding measurement values decreased to 3.8 and 0.9 μSv/h, respectively, when the spherical applicator was inserted into a small water tank. Meanwhile, the ambient dose equivalent rate at 2 m was reduced to the background level when using protective screen.Conclusions:The shielding requirements for a low energy X-ray intraoperative radiotherapy facility are minimal, with low effective energy of X-rays generated by this equipment, but the dose rate close to the unshielded radiation source is high. The shielding scheme of treatment room should be optimized in design and the protective device should be used in a reasonable way.

IgE-mediated food allergy is a common health problem worldwide, and the incidence of food allergy in China is also increasing gradually in the past decades.However, the traditional diagnostic measurements for food allergen specific IgE (sIgE) are based on the in- vivo or in- vitro tests of the intact allergen extracts, with low specificity and sensitivity, as well as limited diagnostic information.Therefore, the clinical diagnosis of food allergies often requires an oral food challenge test, which increases the suffering and risk of patients.Along with the development of component-resolved diagnostics (CRD) of food allergy, the sIgE against a single allergenic component can be measured quantitatively, thus generating the concept of " CRD" , which makes food allergy diagnosis more accurate and helps people distinguish cross allergens, determine the severity of the disease and the risk of severe allergic reactions, and predict the efficacy of immunotherapy.Besides, the diagnostic accuracy would be enhanced significantly and the reliance on oral food challenge tests would be reduced.In this review, the new progress in the diagnosis of common food allergen components would be summarized, and the advantages of CRD would be discussed.