Characteristics And Related Factors Of Visually Related Nerve Injury In Patients With Dysthyroid Optic Neuropathy

Thyroid-associated ophthalmology(TAO)is the most common orbital disease in adults although its pathogenesis is still uncertain.Clinical complications include proptosis,eyelid retraction,exposed keratitis along with dysthyroid optic neuropathy(DON).The latter is one of the most severe complications of TAO,resulting in permanent and irreversible visual field(VF)defects,and consequently,a heavy socioeconomic burden for patients and their families.The onset of DON is often occult and its pathogenesis is complex and multifactorial.Therefore,understanding the underlying mechanisms will be of great benefit to the early prevention and timely treatment of DON.The consensus view is that DON results from microcirculatory disturbances and optic nerve compression secondary to orbital apex congestion.Nonetheless,it is critically important to consider all possible factors that could contribute to the development and progression of DON.It is well known that the thyroid hormone plays a vital role in the growth and development of the nervous system.An increasing number of studies show that thyroid hormone is also vital for maintaining the structure and function of the adult visual cognitive pathway.In our previous study,we observed after long-term follow-up that patients with DON developed hypothyroidism.Moreover,the probability of hypothyroidism in subjects with DON was higher than for non-DON patients and their fluctuations in thyroid hormone levels were also greater.We further investigated the impact of thyroid hormone fluctuation in a rat model and observed some typical manifestations of TAO including pathological changes and optic nerve injury.This analysis raised some key questions relevant to the etiology of TAO and the occurrence of DON.Foremost of these questions was whether abnormalities in thyroid hormone levels were involved in the pathogenesis of DON?If this hypothesis was true,then DON patients should have central system abnormalities.the current study aims to further analyze the relationship between brain function connection abnormalities and optic nerve injury in DON patients,and further,analyze its relationship with thyroid hormone levels.Since the evidence suggests that the thyroid hormone participates in the pathogenesis of DON,a second major question to consider is what is the mechanism involved?Thyroid hormone levels can regulate intraocular pressure and blood pressure and display a circadian rhythm.Consequently,the abnormal fluctuation of 24-hour blood pressure,intraocular pressure,and perfusion pressure had been widely proposed as the mechanism causing optic nerve injury in glaucoma.Therefore,it is possible that thyroid hormone abnormalities may participate in optic nerve injury in TAO patients through abnormalities in blood pressure,intraocular pressure,and/or perfusion pressure.On this basis,the second aim of the current study involved exploring the relationship between changes of 24-hour blood pressure,intraocular pressure,and perfusion pressure and the pathogenesis of DON,and to further analyze the relationship between these indicators and thyroid hormone levels.Together these aims sought to provide clinical evidence for the involvement of thyroid hormone in the pathogenesis of DON.The first partAnalysis of the relationship between brain functional connectivity and optic nerve abnormalities in patients with DON[purpose]To explore the correlation between abnormal brain functional connectivity and optic nerve injury in DON patients using resting-state brain functional connectivity analysis,and to further analyze its correlation with thyroid hormone levels.[methods]Patients diagnosed with TAO in the Eye Hospital of Wenzhou Medical University were recruited to the study.The study was approved by the ethics committee of the Eye Hospital of Wenzhou Medical University.After informed consent,all patients received complete ophthalmic examination according to the EUGOGO standard including CAS scoring,best-corrected visual acuity(BCVA)examination,with data expressed as decimal visual acuity.Humphrey's visual field analyzer was used for visual field examination,Optical Coherence Tomography(OCT)examination,and orbital/brain fMRI examination.fMRI data acquisition and data analysis were completed in the Second Affiliated Hospital of Wenzhou Medical University(Sino American Brain Function Research Center).The patients were divided into two groups according to the MD value of the visual field examination.Those DON patients with MD<-5dB of the average visual field of both eyes were included in the DON group,and those TAO patients with MD?-2dB were included in the non-DON group(nDON group).[results]1.A total of 30 TAO patients with complete data were collected,including 14 males and 16 females,with an average age of 48.79±7.37(40-57)years.There were 16 cases in the DON group and 14 cases in the nDON group.There was no significant difference in age,gender,and education between the two groups.2.The index of orbital apex crowding:the average maximum transverse diameter of medial muscle were 7.17±2.12mm and 6.56±1.89 mm respectively(P=0.121),the average vertical Barrett's muscle index was 57.72±4.95%and 55.44±13.52%respectively(P=0.237),and the average horizontal Barrett's muscle index was 56.17±10.87%;5 0.82 ±11.82%respectively;(P=0.259)in the DON and nDON groups.There was no significant difference between the two groups.3.There was a significant difference in visual field MD between the DON group and the nDON group(P<0.001),but there were no significant differences in retinal nerve fiber layer(RNFL)thickness results using OCT between the two groups.4.Analysis of differences in brain functional connectivity between the two groups4.1 Whole-brain functional connection density analysis showed there were significant differences between the DON and nDON groups,with the DON group showing abnormalities in the right Frontal.Inf.Orb and left Precuneus(P<0.05).Reduced FCD was observed in the right Frontal.Inf.Orb,and increased FCD was observed in the left Precuneus.4.2 analysis of FC based on seed pointsBased on the send-points of the left precuneus,compared with the nDON group,the FC in the DON group was significantly increased(P<0.05),and the increased brain areas included Cuneus.R?Fusiform R?Occipital.sup L,and the left middle temporal gyrus.Based on the send-points of the right Frontal.Inf.Orb,the FC in the DON group decreased significantly(P<0.001).The decreased brain areas include Postcentral.R?Parietal_Inf_L?Cuneus.R?Fusiform R,and Occipital.sup L.5.Correlations between visual field,OCT,and brain functional connectivityCorrelation analysis between visual field,OCT results,and whole-brain FCD analysis shows that there was no correlation between OCT and FCD,but there was a significant correlation between binocular visual field MD and FCD.The MD value of the right visual field was negatively correlated with the FCD of left precuneus-related FCD(R=-0.489,P=0.006),and positively correlated with the FCD of the right Frontal.Inf.Orb(R=0.490,P=0.008).The left visual field MD value was negatively correlated with the FCD of the left precuneus(R=-0.481,P=0.011),and there was a non-significant trend showing a positive association with the right prefrontal orbital gyrus(R=0.273,P=0.168).6.Relationship between thyroid hormone and brain function connectivityWe found a significant correlation between thyroid hormone levels and whole-brain FCD in TAO patients.There was a significant positive correlation between the FCD of the right Frontal.Inf.Orb and T3 and FT3(R=0.485,P=0.048;R=0.528,P=0.021,respectively).TheFCD of the left precuneus showed a positive correlation with TSH(R=0.465,P=0.045).[Conclusion]Patients with DON have visual-related dysfunction of higher cortical functional connections,which is related to optic nerve injury and thyroid hormone levels.The second partAnalysis of the relation of abnormal 24h MOPP/IOP/BP and optic nerve abnormalities in patients with TAO[Purpose]To analyze correlations between 24h MOPP/IOP/BP and optic nerve injury in TAO patients,and to further analyze the correlation with thyroid hormone.To explore the possible mechanism of abnormal 24h MOPP/IOP/BP in the pathogenesis of DON.[Methods]Patients with TAO diagnosed in the Eye Hospital of Wenzhou Medical University were recruited.The study was approved by the ethics committee of the Eye Hospital of Wenzhou Medical University.After obtaining informed consent,patients were hospitalized for examinations including routine ophthalmic history inquiry,bestcorrected visual acuity,exophthalmos,routines slit-lamp examination,fundus examination,visual field,OCT,orbital MRI,and routine thyroid function examination.All patients underwent Goldmann tonometer examination and mercury desktop sphygmomanometer to measure blood pressure over 24 hours(data were acquired at 5,7 and 10 a.m.,and 2,6,and 10 p.m.).PP?MAP,and MOPP were calculated according to the relevant formulas.The maximum-minimum value was used to represent the 24hour fluctuation value in the relevant indicators.Both eyes were included in the study and divided into two groups according to the MD value of visual field examination,namely,those with MD<-2dB of the visual field as the abnormal visual field injury group,and those with MD ?-2dB of the visual field regarded as the normal visual field group.[results]1.A total of 30 patients(60 eyes)were included in this study,including 11 males and 19 females.The average age was 47.97±10.93(26-67)years.The abnormal visual field group included 36/60 eyes and 24/60 eyes were in the normal visual field group.The MD values of the left and right eyes of all patients were-5.5± 7.6db and-6.5±7.6db respectively.There was no significant difference between the two eyes(P=0.562).2.The ocular muscle index in the abnormal visual field group and the normal groups were 57.03%and 51.18%,respectively(P=0.56)while the horizontal ocular muscle index was 50.48%and 48.66%,respectively(P=0.64).The maximum diameter of the medial rectus muscle in the abnormal visual field group and the normal group was 6.24 mm and 5.40mm,respectively(P=0.15).There were no significant differences between the disease and normal groups.3.There was no significant difference in RNFL thickness between the two groups.4.Except for 5 a.m.(P=0.027)and 10 p.m.(P=0.008),there was no significant difference in intraocular pressure and 24-hour intraocular pressure fluctuations between the two groups.5.There were no significant differences in systolic blood pressure,diastolic blood pressure,and pulse PP between the two groups at all time points except for significant differences in pulse pressure at 2 p.m.(P=0.042).6.There was a significant difference between the 24-hour mean ocular perfusion pressure fluctuation(24h-MOPP)values and SD values between the two groups(P=0.033 and 0.008,respectively),and there was a significant negative correlation between the 24h MOPP fluctuation value and the visual field MD value(R=-0.434,P<0.001).7.There was no correlation between thyroid hormone levels and visual field,HRT-?/OCT indexes,but there was a significant correlation between thyroid hormone levelsand diastolic pressure at 7 a.m.(R=0.286 P<0.05),mean perfusion pressure at 7 a.m.(R=0.273 P<0.05),and 24h MOPP fluctuation(R=0.356 P<0.05).[Conclusion]Fluctuations in 24h MOPP are closely related to optic nerve injury in TAO patients and are associated with thyroid hormone levels.