The Visual Prognosis Of Behcet's Disease Uveitis And Its Association Analysis With IL33/ST2 Gene Polymorphism

Part one Clinical features and visual prognosis analysis ofBehcet's uveitisPurpose:To investigate the clinical features and prognostic factors of Behcet s uveitis in north China.Methods:Retrospectively review the medical records of Behcet's uveitis patients presenting to Peking Union Medical College Hospital from January 1998 to December 2018.Results:One hundred and seventy nine Behcet's uveitis(BDU)patients(323 eyes)were included,among which,138 patients(253 eyes)were male,40 patients(70 eyes)were female.Most of these patients had binocular involvement(79.9%,143/179),with a mean age of uveitis onset at 29.07 years.The most frequent type of uveitis was panuveitis.Oral aphthae were the most common extraocular manifestation,followed by dermatological lesions and genital ulcers.The final best corrected visula acuity(BCVA)was 0.05 or less in 81 eyes(25.1%,81/323).And the risks of loss of useful vision(<0.05)within 5 and 10 years for males and females were 47.0%versus 40.0%and 49.9%versus 43.3%,respectively.Male,binocular involvement,rural patients,positive family history and severe oral aphthae were independent risk factors for low vision.Maculopathy(58.8%,190/323)and complicated cataract(55.4%,179/323)were two of the most common ocular complications of BDU patients,and both of which together with optic nerve atrophy were also the independent risk factors for low vision(p<0.001,p<0.001,p=0.007,respectively)Conclusions:Male,rural resident,positive family history,severe oral aphthae,and binocular involvement can serve as predictive factors for poor visual prognosis.Complicate cataract,macular lesions and optic nerve atrophy were the most relevant complications for visual damage.Part two Assessments of retinal vascular changes in eyes with Behcet's uveitisPurpose:To assess the characteristics of parafoveal microvascular abnormalities in Behcet's uveitis using optical coherence tomographic angiography(OCTA).Methods:A retrospective study of Behcet's uveitis patients who underwent OCTA examination in Peking Union Medical College Hospital between April 1,2017 and October 31.2018.Results:A total of 60 consecutive Behcet's uveitis patients(102 eyes)were included.Sixty-two(124 eyes)healthy subjects served as normal control.The vessel density(VD)of both superficial and deep retinal capillary layers,fovea avascular zone(FAZ)area,FAZ perimeter and FAZ acircularity index(Al),were significantly different in BDU eyes as compared to controls and these parameters were all correlated with visual acuity.Capillary disruptions were observed in 30(29.4%)Behcet s uveitis eyes,and macular edema,long disease course were identified as independent risk factors of capillary structural damage.Reduction of retinal capillary VDs were observed during unilateral uveitis attack in both the active and the clinically quiescent fellow eyes.Conclusions:Behcet's uveitis patients had significant OCTA changes that correlated with visual prognosis,and retinal microcirculation changes were exist in both eyes during unilateral Behcet's uveitis attack.Part three Association analysis of Behcet's uveitis and single nucleotide polymorphisms in IL33 and ST2 genesPurpose:To investigate the association between IL33/ST2 pathway gene single nucleotide polymorphism(SNP)and Behcet's disease(BD)uveitis in China.Methods:Genome DNA were extracted from the peripheral blood of 595 BD uveitis patients and 586 controls.The genotypes of 18 SNPs(rs1048274,rs7044343,rs2058660,rsll792633,rs2210463,rs12712142,rs6543115,rs2310220,rs1891385,rs13424006,rs3821204,rs7037276,rs16924161,rs10975509,rs12712135,rs7025417,rs10118795,rs10975519)in IL33/ST2 pathway were analysed by matrix assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF MS).PLINK and Hploview were used for association analysis of SNPs between BD patients and controls,and among different types of BD patients.Results:The allele frequency of rs3821204(Pc=0.033)was significantly different between BD and control groups,which was persistent in the additive model(Pc=0.029).The allele and genotype frequencies of rs2210463,rs1048274,rs7044343 were all different between complete and incomplete BD groups.Significant associations were found between rs2210463,rs1048274,rs7044343 and complete BD in both additive and recessive models,and between rsll792633 and complete BD in recessive model.A haplotype consisting of six SNPs of ST2 gene(rs6543115 G-rs2310220 A-rs3821204 G-rs12712142 Ars13424006 T-rs2058660 A)was also found,which confers protective effect from BD.Conclusions:The IL33/ST2 gene SNPs were involved in the pathogenesis and phenotype developments of BD uveitis.The genetic basis of BD patients may be different between complete type and incomplete type.