The Related Study Of The Visually Guided Saccade In Hyperthyreosis Patients With No Pre-existing Eye Damage

Backgroud:Hyperthyroidism refers to high thyroid function status,It can lead to high metabolic syndrome and systemic symptoms of multiple systems.Hyperthyroidism can also cause eye damage.Eye diseases caused by hyperthyroidism belong to thyroid-associated ophthalmopathy(TAO).TAO is the complex orbital diseases caused by many factors.Pathogenesis is not clear at present,general idea that consists of common genetic factors,immunology and external environment.TAO progress slowly,it couldn't easily be found early.As the disease progress,chronic fibrosis lead the serious complications as a corneal ulcer perforation,diplopia,decreased visual function.Treatment of TAO mainly is the use of corticosteroids to control the immune response of the eye.But effect of corticosteroids is better during the course of ocular inflammation symptoms at early stage,or there has been a serious sequelae and chronic fibrosis of patients with poor effect.So the early detection of TAO,is of great significance for timely to carry out the effective treatment.The inspection methods for TAO,mainly are B ultrasonic,CT,MRI and other imaging examination method.But only when the organization of eye or muscle morphological change,TAO can be found.Because the price of these inspection methods is expensive,they are not suitable for as a way of TAO early screening,At present,the lack of sensitive objective examinations for early TAO patients remains a problem.We commonly use classification methods for NOSPECS to judge the stage and severity of thedisease.Lower NOSPECS grading(0-2)status based primarily on eyeball symptoms and signs,which is easily ignored by doctors.And NOSPECS is relatively complex,and exist for diagnosis of patients with TAO may not step by step development,it still has some shortcomings.Saccade is a kind of fast moving eye movement pattern,double eye fast in the same direction,synchronized movements.It Is eyeball of the advanced features of the human.A saccade needs the central nervous,the optic nerve,eye muscle and orbital tissue involved.TAO is a kind of eye disease,since the early pathological changes of organization hyperemia oedema to late fibrosis can be involvement of extraocular muscle and orbital tissue,lead to the change of eye tracking ability,so by checking the eye tracking ability to detect early TAO is a theoretical basis.The study of TAO and saccadic function is not much at past,the results of the existing thought that for patients with severe TAO the saccadic functions were abnormal.For early TAO research is quite limited.At home,there is no related research about TAO of eye tracking ability.Objective:In this study,we try to explore the potential eye damage of the first-episode treatment-naive hyperthyreosis patients without pre-existing eye symptom by using basic visually guided saccade(VGS)first time.Methods:The hyperthyroidism group included 15 first-episode treatment-naive hyperthyroidism outpatients(2 males and 13 females)who were recruited from the First Affiliated Hospital of Anhui Medical University.The NOSPECSclassification of American Thyroid Association of all patients were grade 3 or less(?3)by endocrinologist.15 healthy controls enrolled by advertisements from nearby districts,with no personal history of thyroid or other endocrine-related diseases.All participants in our study did not have myopia,astigmatism,other ametropia,epilepsy,mental retardation,severe physical disease.The age and gender of two groups were similar.An IVIEW X HISPEED eye tracker(Senso Motoric Instruments Gmb H,Germany)was used to record participants' eye movements.Experimental paradigm is VGS.The following parameters were recorded during each saccade: amplitude,duration,latency,peak velocity(PV),peak acceleration and peak deceleration.Saccade PV and amplitude can be fitted in main sequence equation[equation-1:Peak Velocity = Vmax *(1-e^(-Amplitude/c))].In this equation,Vmax is the asymptotic value of the PV of the saccades of big amplitude,c is the amplitude constant.The nonlinear regression procedure was used on each group to estimate the Vmax and constant c to fit the main sequence.General linear model(GLM)was used to find the differences on latency,peak acceleration and peak deceleration between the groups.Saccade latency,peak acceleration and peak deceleration were set as the dependent variables,the PV,duration,amplitude as covariates,pair wise comparisons between groups was using the Bonferroni correction method.Results:1.The Vmax values of control group and hyperthyroidism group were 438.47+55.46°/s and486.10+51.49°/s,the Vmax values were found to be significantly different between two groups(Mann-Whitney U test,Z =-2.053,P = 0.040).2.Results of the GLM-based analysis at amplitude of 10.819°,PV value of 311.587°/s,and in a time duration of 61.94 ms,indicated that the saccade latency of the control group and hyperthyroidism group was 234.601 ms(95% CI = [230.497,238.705]),and 223.364 ms(95% CI = [219.245,227.482]),respectively,a significant difference was found between the saccade latency of both groups(P<0.001).Similarly,the peak acceleration in control group and hyperthyroidism group was 13959.973°/s2(95% CI = [13894.610,14025.337]),and 14127.205°/s2(95% CI = [14061.606,14192.804]),respectively,peak acceleration was also found to be significantly difference between the two groups(P<0.001).The peak deceleration in control group and hyperthyroidism group was-10194.008°/s2(95% CI =[-10296.046,-10091.970]),and-10160.784°/s2(95% CI = [-10263.189,-10058.378]),respectively,and no significant difference was observed between in the peak deceleration of the two groups(P = 0.662).Conclusions:Compared with normal healthy controls,we found that hyperthyreosis patients showed a significant difference in the dynamics of saccades during VGS.Saccade tracking examination may have a potential value for the early detection of TAO.Backgroud:TAO is closely associated with hyperthyroidism.90% of the TAO is caused by hyperthyroidism,but the relationships between TAO and hyperthyroidism severity,duration,thyroid function are not clear,also we don't know very well TAO pathogenesis and development process.Due to the lack of effective therapy on the etiologies of TAO at present,the early treatment purpose is controlling the phases of immune inflammation and the late purposes are improving the face and protecting the visual function.For TAO diagnosis standard is still not unified,the lack of sensitive objective examinations for early TAO patients remains a problem.Eye tracking technology has good sensitivity for the early diagnosis of various diseases,including Parkinson's disease,systemic sclerosis,hyperactivity,Alzheimer's disease,schizophrenia.It has attracted much attention in the field of neural psychology and psychiatry.The study of TAO and saccadic function is not much at past,but some evidences have demonstrated that the eye movement functional damage could be found in hyperthyroidism.In our previous studies we explored the potential eye damage of the first-episode treatment-naive hyperthyreosis patients without pre-existing eye symptom by using basic visually guided saccade(VGS).The results showed the patients existed abnormal eye movements,It proved the relationships between the hyperthyroidism and eye tracking ability.This is the first attempt in the field by eyetracking technology in China.Objective:In order to further explore the relationship between hyperthyroidism and TAO,in this study we will continue to use the saccade tracking examinationto find the damage of eye tracking ability in hyperthyroidism patients with no pre-existing eye damage,and we try to search sensitiveindicators which can be used to describe eye tracking ability,and the related factors of abnormal eye tracking ability in hyperthyroidism.Methods:The hyperthyroidism patients were randomly recruited from endocrine clinic in the First Affiliated Hospital of Anhui Medical University.The NOSPECS classification of American Thyroid Association of all patients were grade 3 or less(?3)by endocrinologist.The healthy controls enrolled by advertisements from nearby districts,with no personal history of thyroid or other endocrine-related diseases.All participants in our study did not have myopia,astigmatism,other ametropia,epilepsy,mental retardation,severe physical disease.All participants were divided into the control group,the hyperthyroidism group without drug treatment,the hyperthyroidism group with drug treatment.The age and gender of three groups were similar.An IVIEW X HISPEED eye tracker(Senso Motoric Instruments Gmb H,Germany)was used to record participants' eye movements.Experimental paradigm is VGS.The following parameters were recorded during each saccade: amplitude,duration,latency,peak velocity(PV),peak acceleration and peak deceleration.Saccade PV and amplitude can be fitted in main sequence equation [equation-1:Peak Velocity = Vmax *(1-e^(-Amplitude/c))].In this equation,Vmax is the asymptotic value of the PV of the saccades of big amplitude,c is the amplitude constant.The nonlinear regression procedure was used on each group to estimate the Vmax and constant c to fit the main sequence.General linear model(GLM)was used to find the differences on latency,peak acceleration and peak deceleration between the groups.Using the equations of acceleration asymmetric index(AAI),we calculate each saccadic AAI,and calculated Spearman correlationcoefficient of the duration of saccadic and AAI(RAD)between groups.We compared the difference of RAD by the Mann-Whitney U inspection.For studying the related factors of RAD in hyperthyroidism,we made Spearman correlation analysis between RAD and duration,T3,T4,TSH.We do regression analysis for the RAD and duration for 6 months.Results:1.The Vmax values of control group is 443.859°/s(95% CI =433.719-453.999),the Vmax values of the hyperthyroidism without drug treatment and the hyperthyroidism with drug treatment were 490.736°/s(95% CI =478.656-502.817)and 458.159°/s(95% CI=443.169-473.150).The Vmax values were found to be significantly different between control group and the hyperthyroidism group without drug treatment,nosignificant difference was observed between control group and the hyperthyroidism group with drug treatment.2.Results of the GLM-based analysis at amplitude of 10.155°,PV value of 300.996 °/s,and in a time duration of 60.06 ms,indicated that the saccade latency of three groups were238.587 ms(95% CI = [230.792,246.382])? 237.437ms(95% CI = [228.608,246.267])and 240.716ms(95% CI = [233.168,248.263]),no significant difference was found between the saccade latency of three groups.The peak acceleration of three groups were13690.682 °/s2(95% CI = [13610.496,13770.868])? 13848.965 °/s2(95% CI =[13758.137,13939.794])and 13741.763 °/s2(95% CI = [13664.121,13819.406]).Peak acceleration was also found to be significantly difference between control group and the hyperthyroidism group without drug treatment(P=0.01).The peak deceleration of three groups were-10084.399 °/s2(95% CI = [-10207.519,-9961.278])?-10480.185 °/s2(95%CI = [-10619.647,-10340.724])and-10317.593 °/s2(95% CI = [-10436.808,-10198.377]).Comparing in pairs,significant difference was observed between control group and the hyperthyroidism group without drug treatment or the hyperthyroidism group with drug treatment(P<0.01)and no significant difference was observed between the two hyperthyroidism groups.3.Comparing in pairs of three groups,RAD were found to be significantly different between control group and the hyperthyroidism group with drug treatment(Mann-Whitney U test,Z =-2.676,P = 0.007),no significant difference was observed between control group and the hyperthyroidism group without drug treatment(Mann-Whitney U test,Z =-1.141,P =0.254),no significant difference was observed between the two hyperthyroidism groups.(Mann-Whitney U test,Z =-1.699,P = 0.089).4.The RAD values of control group and the hyperthyroidism were 0.439±0.196 ?0.562±0.193(P = 0.05).RAD was positively correlated with T3 and T4,and negatively correlated with TSH.To learn the relationship between RAD and course,we respectively carried on the correlation analysis on hyperthyroidism patients who the course of the disease was over 3 months,over 6 months and over 12 months.we found that RAD was associated with the course of in hyperthyroidism patients who the course was over 6months and 12 months.5.We used the nonlinear regression on hyperthyroidism patients who the course of the disease was less than or equal to 6 months,The fitting equation for Y=0.296+0.189*x-0.034*x*x,R2=0.261.We used a linear function fitting on hyperthyroidism patients who the course of the disease was longer than 6 months,The fitting equation for Y =0.266 + 0.006*x,R2=0.258.Conclusions:1.Compared with control group,we found that the hyperthyroidism group without drug treatment and the hyperthyroidism group with drug treatment showed a significant difference in the dynamics of saccades during VGS.The patients of the hyperthyroidism group without drug treatment showed faster Vmax,the peak acceleration and the peak deceleration.The patients of the hyperthyroidism group with drug treatment showed faster Vmax and the peak deceleration.RAD of the hyperthyroidism group with drug treatment was lower than control group.2.RAD of hyperthyroidism patients was positively correlated with T3 and T4,and negatively correlated with TSH.3.RAD was positive correlation with progression in hyperthyroidism patients who the course of the disease was over 6 months and 12 months.RAD of hyperthyroidism patients who the course of the disease was less than or equal to 6 mouths was nonlinear correlation with the course,RAD of hyperthyroidism patients who the course of the disease was longer than 6 mouths was Linear correlation with the course.